Clinicians frequently stress the importance of maintaining good oral health for multiple reasons, including its link to systemic health. Because periodontal treatment reduces inflammation in oral tissues, some hypothesize it may positively affect systemic outcomes by reducing inflammation in the body. A significant number of systematic reviews (SRs) and meta-analyses (MAs) have evaluated the effect of periodontal treatment on systemic outcomes. However, inconsistent findings and questionable methodological rigor make drawing conclusions difficult. We conducted a systematic review of reviews that studied the effect of nonsurgical periodontal treatment on systemic disease outcomes. We report on outcomes evaluated, categorizing them as biomarkers, and surrogate or clinical endpoints. In addition, we used A MeaSurement Tool to Access systematic Reviews 2 (AMSTAR 2) to evaluate the methodological quality of the reviews. Of the 52 studies included in our review, 21 focused on diabetes, 15 on adverse birth outcomes, 8 on cardiovascular disease, 3 each on obesity and rheumatoid arthritis, and 2 on chronic kidney disease. Across all studies, surrogate endpoints predominated as outcomes, followed by biomarkers and, rarely, actual disease endpoints. Ninety-two percent of studies had “low” or “critically low” AMSTAR 2 confidence ratings. Criteria not met most frequently included advance registration of the protocol, justification for excluding individual studies, risk of bias from individual studies being included in the review, and appropriateness of meta-analytical methods. There is a dearth of robust evidence on whether nonsurgical periodontal treatment improves systemic disease outcomes. Future reviews should adhere more closely to methodological guidelines for conducting and reporting SRs/MAs than has been the case to date. Beyond improved reviews, additional rigorous research on whether periodontal treatment affects systemic health is needed. We highlight the potential of large-scale databases containing matched medical and dental record data to inform and complement future clinical research studying the effect of periodontal treatment on systemic outcomes.