Background <p>Sedentary behavior has become a common way of life in modern society, and is correlated with many chronic diseases. Exercise intervention is regarded as an effective measure to reduce the negative effects of sedentary behavior, however, comprehensive network meta-analyses comparing the relative effectiveness of different exercise programs on cardiovascular and metabolic indicators in sedentary adults are lacking.</p> Objective <p>The regulatory effects of different exercise programs on physiological indicators such as blood glucose, blood lipid, and blood pressure in sedentary adults were analyzed through network meta-analysis to provide a basis for optimizing exercise programs.</p> Methods <p>This study systematically searched the PubMed, Web of Science, Embase, and Cochrane databases for randomized controlled trials on sedentary adults published up to November 14, 2024. The risk of bias was evaluated using ROB2.0, and network meta-analysis was conducted using Stata 18.0 and R 4.2.2 software. The standardized mean difference (SMD) was used as the effect size, and different exercise programs were ranked by SUCRA.</p> Results <p>47 studies were included in this study, involving 2,355 research subjects. In terms of regulating blood pressure, combined exercises (aerobic combined with strength training (AT + ST) and aerobic combined with resistance training (AT + RT)) were significantly superior to the single exercise program, especially in decreasing both systolic and diastolic blood pressures. Pilates exercise (PT) ranked first (79.6%) in improving systolic blood pressure. As for blood lipids, high-intensity interval training (HIIT) reduced total cholesterol the most (83.4%). AT + ST had a significant advantage (86.7%) in increasing high-density lipoprotein cholesterol (HDL-C), and Tai Chi ranked first (80.4%) in improving low-density lipoprotein cholesterol (LDL-C). Regarding blood glucose metabolism, PT and functional training (FT) showed the best effects in improving glucose levels (85.2% and 83.8%), Tai Chi performed outstandingly in improving glycated hemoglobin (93.9%), and AT + RT had a significant effect in regulating insulin levels (94.7%). 85% of the studies were evaluated as having a low bias risk, and the funnel plot showed no significant publication bias.</p> Conclusions <p>The regulatory effects of different exercise programs on metabolic indicators in sedentary adults vary. The combined exercise programs have a significant effect in improving blood pressure and blood lipids, and HIIT is more effective in regulating blood glucose. Based on these findings, individualized demands and target health indicators should be considered when formulating exercise intervention programs for sedentary adults.</p>