The aim of this study was to compare the metabolic benefits of diabetes-specific formulas (DSF) high in monounsaturated fatty acids (MUFA) with standard formulas (STDF) in adult patients with type 1, type 2 diabetes or stress-induced hyperglycaemia. A systematic review and meta-analysis were conducted through a literature search using different electronic databases from the index date to December 2018. We included randomised controlled trials that assessed the health benefits of high MUFA DSF vs STDF. Included outcomes were glycaemic control, lipid metabolism and tolerance. Effect sizes were calculated as standardised mean differences (SMDs) (<0.4 were considered small, 0.4–0.7 moderate and >0.7 large). This systematic review was registered as CRD42018108931 on Prospero. Of 385 references reviewed, 18 studies involving 845 adults met our inclusion criteria and contributed to the meta-analysis. Use of a high MUFA DSF compared with a STDF was associated with a statistically significant decrease in peak of postprandial glucose SMD −1.53, 95% confidence interval (CI) −2.44 to −0.61, incremental glucose response (SMD −1.19, 95% CI −1.71 to −0.68), area under the curve of plasma insulin (SMD −0.65, 95% CI −1.03 to −0.26), mean blood glucose level (SMD −0.41, 95% CI −0.63 to −0.19), glycosylated haemoglobin (HbA1c) change (SMD −0.63, 95% CI −1.21 to −0.05), glucose variability (SMD −0.93, −1.55 to −0.31), mean administered insulin dose (SMD −0.49, 95% CI −0.85 to −0.14), mean blood triglycerides (SMD −0.34, 95% CI −0.65 to −0.03) and increase of mean blood high-density lipoproteins (SMD +0.42, 95% CI 0.08 to 0.76). Non-significant differences were found for tolerance odds ratio (OR) 0.95, 95% CI 0.87 to 1.05. This meta-analysis shows that a DSF (oral supplements and tube feeds) high in MUFAs can improve glucose control and metabolic risk factors among patients with diabetes or stress-induced hyperglycaemia compared with a STDF.