Objectives: Chronic cardiovascular diseases, cancer, chronic respiratory diseases and diabetes are the four major groups of non-communicable diseases (NCDs) and the main cause of mortality worldwide. Pilates has been described as an effective intervention to promote healthy behaviors and physical activity in people with chronic diseases. However, the evidence of its effects in NCDs have not been systematized. We investigated the effects of Pilates in the four major groups of NCDs. Design: A systematic review was performed. Searches were conducted on Cochrane Library, EBSCO, PubMed, Science Direct, Scopus and Web of Science databases. Studies were rated with the quality assessment tool for quantitative studies. As a meta-analysis was not possible to conduct, a best-evidence synthesis was used. Results: Twelve studies, mostly of moderate quality, were included with 491 participants (78.6% females; age range 13-70 years old) with breast cancer (n = 3), diabetes (n = 3), chronic stroke (2 years post stroke) (n = 2), chronic obstructive pulmonary disease (n = 1), cystic fibrosis (n = 1), heart failure (n = 1) and arterial hypertension (n = 1). The best-evidence synthesis revealed strong evidence for improving exercise tolerance; moderate evidence for improving symptoms, muscle strength and health-related quality of life and limited or conflicting evidence on vital signs, metabolic parameters, body composition, respiratory function, functional status, balance, flexibility and social support. Conclusions: Pilates should be considered for patients with NCDs, as it improves exercise tolerance. Future studies with robust methodologies are still needed to clarify its effectiveness on outcomes with moderate, limited or conflicting evidence and to establish the most suitable intervention protocol.