Objective To observe the effects of dapagliflozin versus saxagliptin on inflammatory markers and renal function in elderly patients with type 2 diabetes mellitus (T2DM). Methods A total of 144 elderly T2DM patients admitted to the Affiliated Hospital of Xuzhou Medical University during September 2018 to November 2020 were prospectively recruited, and then randomly divided into dapagliflozin group and saxagliptin group. Excluding the cases withdrawn from the study or lost to follow-up, 50 patients in the dapagliflozin group and 67 patients in the saxagliptin group were finally included in the statistics. The changes of body mass, blood pressure, blood glucose, inflammatory markers, renal function and adverse events were compared between the two groups. SPSS statistics 23.0 was used for statistical analysis. Data comparison was performed using student′s t test, Mann-Whitney U test, Wilcoxon signed-rank test, Chi-square test, or Fisher exact probability test depending on date types. Spearman nonparametric correlation analysis was adopted to evaluate the relationship of neutrophil/lymphocyte ratio (NLR), lymphocyte/monocyte ratio (LMR), and monocyte/high-density lipoprotein cholesterol ratio (MHR) with renal function. Results After 24 weeks of treatment, more obvious declines of body mass, body mass index, systolic blood pressure, diastolic blood pressure, fasting plasma glucose, 2h postprandial blood glucose, glycosylated hemoglobin A1c, MHR, and C-reactive protein (CRP) level were observed in the dapagliflozin group than the saxagliptin group (P<0.05). The incidence of adverse events was 6.0% (3/50) in the dapagliflozin group, and 4.5% (3/67) in the saxagliptin group, and there was no statistical difference between the two groups (P>0.05). NLR was positively correlated with age, CRP and serum creatinine (SCr) (r=0.229,0.214,0.223, P＜0.05). LMR had negative correlation with age, body mass, CRP and SCr (r=-0.261, -0.202, -0.184, -0.188, P<0.05). There was positive correlation of MHR with age, body mass, CRP, SCr, serum uric acid and Cystatin C (r=0.256,0.305,0.265,0.291,0.204,0.298, P<0.05). Conclusion For the elderly T2DM patients, both dapagliflozin and saxagliptin effectively control the blood glucose, with few adverse events. Dapagliflozin is superior to saxagliptin in body mass loss, decrease of blood pressure, reduction of inflammatory reaction and improvement of renal function.