Objectives: To examine the effect of aerobic and resistant exercise intervention on inflammaging in middle-aged and older adults with type 2 diabetes mellitus (T2DM) using inflammatory cytokines, such as interleukin (IL)-1 β, IL-6, tumor necrosis factor-α (TNF-α), and C-reactive protein (CRP) as biomarkers. Design: Systematic review and meta-analysis. Setting and participants: Middle-aged and older adults with T2DM in the community. Methods: Articles were searched from 8 electronic databases. Randomized control trials (RCTs) published in English, from inception to October 31, 2021, were included in this review. Two authors conducted data extraction and quality appraisal independently following guidelines in the Cochrane Handbook for Systematic Reviews of Interventions. Meta-analysis was conducted using Review Manager. Heterogeneity was investigated using subgroup and sensitivity analysis. Results: This review included 14 RCTs. The meta-analysis showed significant improvement in IL-6 [Z = 3.05; 95% confidence interval (CI): -3.60 to -0.79; P = .002], CRP (Z = 2.44; 95% CI: -0.55 to -0.06; P = .01) and TNF-α levels (Z = 2.96; 95% CI: -2.21 to -0.45; P = .003) post-exercise programs. Subgroup analysis revealed that combined aerobic and resistance exercises and long-term exercises have more significant improvement to the outcomes than usual care. Based on the Grades of Recommendation, Assessment, Development and Evaluation system, considerable risk of bias and low level of certainty were revealed in all biomarker outcomes. Conclusions and implications: Exercise intervention is effective in improving inflammatory, metabolic, and lipid markers in middle-aged and older adults with T2DM. By modifying the levels of these markers with exercise, inflammation and insulin resistance can be improved. Long-term, combined aerobic and resistance exercise interventions have more significant effect on biomarkers. The small sample size of this meta-analysis limited the generalizability of the results. Future studies can consider adopting a more optimized exercise regimen to achieve effective T2DM management in middle-aged and older adults. Similar studies should expand to other populations and larger sample sizes to explore replicability of these effects. Keywords: Aerobic exercises; C-reactive protein; interleukin-6; older adult; resistance exercises; type 2 diabetes mellitus.