N-of-1 trials provide a higher level of evidence than randomized controlled trials for determining which treatment works best for an individual, and the design readily accommodates testing of personalized nutrition. The aim of this systematic review was to synthesize nutrition-related studies using an N-of-1 design. The inclusion criterion was adult participants; the intervention/exposure was any nutrient, food, beverage, or dietary pattern; the comparators were baseline values, a control condition untreated or placebo, or an alternate treatment, alongside any outcomes such as changes in diet, body weight, biochemical outcomes, symptoms, quality of life, or a disease outcome resulting from differences in nutritional conditions. The information sources used were Medline, Embase, Scopus, Cochrane Central, and PsychInfo. The quality of study reporting was assessed using the Consort Extension for N-of-1 trials (CENT) statement or the STrengthening Reporting of OBservational Studies in Epidemiology (STROBE) guidelines, as appropriate. From 211 articles screened, a total of 7 studies were included and were conducted in 5 countries with a total of 83 participants. The conditions studied included prediabetes, diabetes, irritable bowel syndrome, weight management, and investigation of the effect of diet in healthy people. The quality of reporting was mostly adequate, and dietary assessment quality varied from poor to good. The evidence base is small, but served to illustrate the main characteristics of N-of-1 study designs and considerations for moving research forward in the era of personalized medical nutrition therapy.