The overweight person swapped diets with the underweight person. While the underweight person was suddenly given more food than they would usually eat in a few days at one meal, the overweight person was usually given tea, coffee, a small snack, or nothing sometimes. Most of the underweight people were unable to finish their meal, though occasionally the overweight people also refused or struggled to eat their meals, usually after having been in the feeding clinic for a few days. Occasionally both were allowed to leave the feeding clinic for a meal swap, if it was part of both of the participants' diets.

In earlier series, the show featured a food tube for each person. The tube contained what each person ate and drank in the span of one week.

Usually Dr Jessen used shock tactics to demonstrate how poor someone's diet was. Both participants were occasionally shown the extent of their poor diet - for example, through bags of sugar. The "superskinny" would usually be shown pictures of their body and be told about the drastic long-term health effects. In the second series, the "supersizer" was sent to meet a woman named Lisa, whose obesity had meant that she could no longer care for herself and was receiving an operation because of her weight. In later series, the "supersizer" was sent to the United States to visit someone that was heavier than they were. It was used as a shock tactic to show the "supersizer" what they could become if they did not stop their unhealthy lifestyles.

The show also featured Anna Richardson in the 1st, 2nd, and 3rd series, who in the first series examined new methods to lose weight by trying diets she found on the Internet, some of which had shocking side effects. For example, Anna attempted Laser lipolysis, which went drastically wrong and resulted in severe bruising. Also, she discovered Diabulimia and spoke to Isabelle Caro, a French actress, renowned for her underweight figure and anorexia campaign. In the second series, Anna recruited a group of "flab-fighters" - women who wanted to lose weight and whose weight was tracked weekly - and she visited Los Angeles to discover ways A-listers would lose weight. The same series also saw a group of four anorexic women attempt to overcome their eating disorder through eating and preparing foods they would usually avoid with the help of a leading eating disorder specialist. In later series, formerly anorexic journalist Emma Wolf interviewed a number of people who had experienced the effects of eating disorders.

The second, third and fourth series also introduced a section whereby a group of people recovering from eating disorders (the second and third series featured people exclusively suffering from anorexia nervosa, while the fourth included a mixture of eating disorders) were overwatched by a specialist psychiatrist and dietician Ursula Philpot who co-presented Supersize vs Superskinny and who worked to challenge their issues with food.

During the first series in 2008, one feature involved Gillian McKeith, who tried to find a way to "ban big bums" in the UK. She tested out different exercises to tone the buttocks of different groups of ladies, and made a leader board for the most effective.

In 2011, a 4-episode children's version titled Supersize vs Superskinny Kids was produced and aired between 21 and 25 March 2011.

• Supersize vs Superskinny on Channel 4
• Supersize vs Superskinny Kids on Channel 4
• Supersize vs Superskinny at IMDb  
• Review, Leicester Mercury