Abstract Background Dexamethasone is commonly used for antiemesis in surgical patients. It has been confirmed that long-term steroid use increases blood glucose level in both diabetic and non-diabetic patients, it is unclear how a single dose of intravenous dexamethasone used pre/intraoperatively for postoperative nausea and vomiting (PONV) prophylaxis would influence the blood glucose and wound healing in diabetic patients. Methods The Pubmed, Cochrane Library, Embase, Web of Science databases, CNKI and Google Scholar were searched. The articles reporting a single dose dexamethasone administered intravenously for antiemesis in surgical patients with diabetes mellitus (DM) were included. Results Nine randomized controlled trials (RCTs) and 7 cohort studies were included in our meta-analysis. The results showed that dexamethasone increased glucose level intraoperatively (MD: 0.439, 95% CI: 0.137–0.581, I² = 55.7%, P = 0.004), at the end of surgery (MD: 0.815, 95% CI: 0.563–1.067, I² = 73.5%, P = 0.000), on postoperative day (POD) 1 (MD: 1.087, 95% CI: 0.534–1.640, I² = 88%, P = 0.000), on POD 2 (MD: 0.501, 95% CI: 0.301–0.701, I² = 0%, P = 0.000), and increased peak glucose level within 24 hours of surgery (MD: 2.014, 95% CI: 0.503–3.525, I² = 91.6%, P = 0.009) compared with control. It indicated that dexamethasone caused the increase of perioperative glucose level at different time points by 0.439 to 1.087 mmol/L (7.902 to 19.566 mg/dL), and the increase of peak glucose level within 24 hours of surgery by 2.014 mmol/L (36.252 mg/dL) compared with control. Dexmethasone had no impact on wound infection (OR: 0.797, 95%CI: 0.578–1.099, I² = 0%, P = 0.166) and healing (P < 0.05). Conclusion Dexamethasone could increase blood glucose by only 2.014 mmol/L (36.252 mg/dL) of peak glucose level within 24 hours of surgery in surgery patients with DM, the increase of glucose level at each time point perioperatively was even lower, and had no effect on wound healing. Thus, dexamethasone with a single dose could be safely used for PONV prophylaxis in diabetic patients. Trial registration The protocol of this systematic review was registered in INPLASY with the registration number INPLASY202270002.