BACKGROUND: People living with chronic conditions such as diabetes turn to peers on social media to obtain and share information. Although social media use has grown dramatically in the past decade, little is known about its implications for the relationships between people with chronic conditions and health care professionals (HCPs). OBJECTIVE: We aimed to systematically review the content and quality of studies examining what the retrieval and sharing of information by people with chronic conditions on social media implies for their relationships with HCPs. METHODS: We conducted a search of studies in MEDLINE (Ovid), Embase (Ovid), PsycINFO (Ovid), and CINAHL (EBSCO). Eligible studies were primary studies; examined social media use; included adults with any type of diabetes, cardiovascular diseases that are closely linked with diabetes, obesity, hypertension, or dyslipidemia; and reported on the implications for people with chronic conditions-HCP relationships when people with chronic conditions access and share information on social media. We used the Mixed Methods Appraisal Tool version 2018 to assess the quality of the studies, and the included studies were narratively synthesized. RESULTS: Of the 3111 screened studies, 17 (0.55%) were included. Most studies (13/17, 76%) were of low quality. The narrative synthesis identified implications for people with chronic conditions-HCP relationships when people with chronic conditions access and share information on social media, divided into 3 main categories with 7 subcategories. These categories of implications address how the peer interactions of people with chronic conditions on social media can influence their communication with HCPs, how people with chronic conditions discuss advice and medical information from HCPs on social media, and how relationships with HCPs are discussed by people with chronic conditions on social media. The implications are illustrated collectively in a conceptual model. CONCLUSIONS: More evidence is needed to draw conclusions, but the findings indicate that the peer interactions of people with chronic conditions on social media are implicated in the ways in which people with chronic conditions equip themselves for clinical consultations, evaluate the information and advice provided by HCPs, and manage their relationships with HCPs. Future populations with chronic conditions will be raised in a digital world, and social media will likely remain a strategy for obtaining support and information. However, the generally low quality of the studies included in this review points to the relatively immature state of research exploring social media and its implications for people with chronic conditions-HCP relationships. Better study designs and methods for conducting research on social media are needed to generate robust evidence.