Melioidosis is an under-recognized fatal disease in humans, caused by the Gram-negative bacterium Burkholderia pseudomallei. Globally, more than 35,000 human melioidosis cases have been reported since 1911. Soil acts as the natural reservoir of B. pseudomallei. Humans may become infected by this pathogen through direct contact with contaminated soil and/or water. Melioidosis commonly occurs in patients with diabetes mellitus, who increase the occurrence of melioidosis in a population. We carried out a systematic review and meta-analysis to investigate to what extent diabetes mellitus affects the patient in getting melioidosis. We selected 39 articles for meta-analysis. This extensive review also provided the latest updates on the global distribution, clinical manifestation, preexisting underlying diseases, and risk factors of melioidosis. Diabetes mellitus was identified as the predominant predisposing factor for melioidosis in humans. The overall proportion of melioidosis cases having diabetes was 45.68% (95% CI: 44.8–46.57, p < 0.001). Patients with diabetes mellitus were three times more likely to develop melioidosis than patients with no diabetes (RR 3.40, 95% CI: 2.92–3.87, p < 0.001). The other potential risk factors included old age, exposure to soil and water, preexisting underlying diseases (chronic kidney disease, lung disease, heart disease, and thalassemia), and agricultural activities. Evidence-based clinical practice guidelines for melioidosis in patients with diabetes mellitus may be developed and shared with healthcare professionals of melioidosis endemic countries to reduce morbidity.