People with diabetes mellitus (DM) are at an increased risk for developing dry eye disease (DED). However, the mechanisms underlying this phenomenon remain unclear. Recent studies have found that the ocular surface microbiota (OSM) differs significantly between patients with DED and healthy people, suggesting that OSM dysbiosis may contribute to the pathogenesis of DED. This hypothesis provides a new possible explanation for why diabetic patients have a higher prevalence of DED than healthy people. The high-glucose environment and the subsequent pathological changes on the ocular surface can cause OSM dysbiosis. The unbalanced microbiota then promotes ocular surface inflammation and alters tear composition, which disturbs the homeostasis of the ocular surface. This "high glucose-OSM dysbiosis" pathway in the pathogenesis of DED with DM (DM-DED) is discussed in this review.