This study is aimed at assessing the scientific evidence on the effect of the intake of sesame seeds and derivatives on oxidative stress of individuals with systemic hypertension, dyslipidemia, and type 2 diabetes mellitus. A systematic review was conducted in seven databases (Lilacs, PubMed, ISI Web of Knowledge, Cochrane Library, Scopus, Trip Database, and Scielo) from September 2013 to January 2014. Clinical trials on the intake of sesame seeds and derivatives assessing the outcomes related to oxidative stress were retrieved. The risk of bias in the results of the studies selected was assessed according to the criteria of the Cochrane Handbook for Systematic Reviews of Interventions. This review included seven clinical trials showing that the intake of sesame resulted in the increase in enzymatic and nonenzymatic antioxidants, as well as in a reduction in oxidative stress markers. This was mainly observed with the use of sesame oil for hypertensive individuals during 2 months and black sesame meal capsules for prehypertensive individuals during four weeks. Most studies involved a small number of participants, sample size being considered a limiting factor for this review. In addition, a significant heterogeneity was observed in the type of population studied and the type of sesame and derivatives used, as well as their amount. The follow-up time was considered a limiting factor, because it varied in the different studies. The high risk of randomization and blinding biases found in the studies assessed determines lower scientific evidence of the results. Despite the limitations and biases identified in this systematic review, sesame showed relevant effects on oxidative stress, suggesting it could increase the antioxidant capacity.