Sweet potato (Ipomoea batatas) thrives in a wide range of climates and is high in fibre, vitamins and minerals. There is increasing evidence that sweet potato consumption can positively affect human health. This systematic review aimed to summarise nutritional-related health outcomes of sweet potato intake among healthy people and people with chronic diseases by reviewing human intervention trials. A total of 22 articles met the inclusion criteria, which examined the effects of sweet potato on vitamin A intakes and status (n = 8), glycemic markers and anthropometric parameters (n = 6), hepatic biomarkers (n = 3) and blood pressure (n = 1), iron absorption (n = 1), constipation (n = 1), nitrogen balance (n = 1), and sex hormones (n = 1). In the included studies, sweet potato consumption appears to improve vitamin A status, blood glucose levels, blood pressure, iron absorption, constipation, liver function and nitrogen balance. However, the evidence base is limited and future research in long-term, well-designed, randomised controlled trials are needed to establish cause-and-effect relationships with these health effects of sweet potato consumption. The functional properties of the bioactive compounds in sweet potatoes require further investigation to establish their ability to manage chronic disease when consumed in high amounts.