Null was raised in Parkersburg, West Virginia, with his two brothers. He holds an Associate Degree in Business Administration as well as a Bachelor of Science degree from Thomas Edison State College in Trenton, New Jersey. He has a PhD in "Interdisciplinary Studies" from Union Institute & University, a private college that gives degrees by correspondence from Cincinnati, Ohio. According to Null, his thesis was titled, "A Study of Psychological and Physiological Effects of Caffeine on Human Health." Union Institute & University is accredited by the North Central Association of Colleges and Schools, but its accreditation does not cover awarding of PhDs in the sciences, only in the humanities. Null is a New York State Registered Dietitian and Nutritionist.

Null is best known as a promoter of natural and alternative remedies. He has written or produced more than seventy books, booklets, and audio CDs on the topics of health, wellness, nutrition, and alternative medicine.

Null says he sleeps only two hours a night, promotes vigorous exercise even for the elderly, and says that although "younger people may have enthusiasm...today what they share is a social psychosis. Ninety percent of the people in my support groups are whining all the time."

Gary Null has attacked many facets of mainstream medicine. He argues that physicians are not actively conspiring, but are just trained and conditioned to accept the premises of their profession. Null believes that physicians have an economic interest in sickness maintenance, not prevention. Null co-authored a series of articles on cancer research, new therapies, and political influence for Penthouse, beginning with one entitled "The Great Cancer Fraud". He accused the "medical community of suppressing alternative cancer treatments to protect the medical establishment's solid-gold cancer train." In 1999 Time wrote: "From a young reporter this is to be expected. But two decades later, Null, 54, is still warning of a variety of medical bogeymen out to gull a trusting public."

Gary Null is also a promoter of AIDS denialism, the belief that HIV is harmless or does not exist, and is not the cause of AIDS. Null sells self-produced films on his website that promote AIDS denialism.

Null's syndicated radio talk show, Natural Living with Gary Null, earned eight Silver Microphone Awards (an award presented to radio commercials). The show, which has been on the air for more than 27 years, is the longest-running continuously airing health program in the United States. It broadcast first on WBAI, then on the VoiceAmerica Network and now broadcasts over the Internet on the Progressive Radio Network.

Null has made several self-funded and published documentary films on public policy issues, personal health, and personal development. Null's videos have been aired by PBS during pledge drives, but concern arose within PBS over the sensational claims they contained, with Ervin Duggan, the president of PBS, expressing concern with the network "open[ing] the door to quacks and charlatans." Null implied that his problems with PBS may have been an attempt to silence him, saying: "The guardians of the gates of orthodoxy at PBS... you don't know who their friends are."

Null is the owner of the dietary supplement and media company Gary Null & Associates, Inc. He owns a health food store, Gary Null's Uptown Whole Foods Market, in New York City.

In 2010, Null filed suit against Triarco Industries, a company that manufactured a product called Gary Null's Ultimate Power Meal. Null's suit contends that flawed testing and manufacturing practices led to the inclusion of 1,000 times the daily recommended amount of vitamin D, and that as a result he suffered kidney damage and intense pain.

Many of Null's viewpoints are controversial and he has attracted the attention of Stephen Barrett of the alternative medicine watchdog website, Quackwatch. Barrett criticizes the validity of Null's PhD thesis, his alternative health claims, and several of his commercial products.

The James Randi Educational Foundation, an organization that aims to promote critical thinking, has accused him, together with Wayne Dyer, of "dealing in nonsense", promoting the notion of eternal youth, and prescribing magnets and "other medieval tools" to prevent aging.

In 2009, Null was criticized for his remarks as a keynote speaker at a political rally against mandatory H1N1 influenza vaccination at the New York State Capitol in Albany, New York. New York State Health Commissioner Richard Daines said, "Like any number of things he’s wrong about, he’s wrong about that."