To assess the associations between the creatinine-to-body weight (Cre/BW) ratio and reversion to normoglycemia mediated by the aspartate aminotransferase-to-alanine aminotransferase (De Ritis) ratio. This retrospective cohort study included 24,884 prediabetic participants from health check-ups in 32 regions across 11 Chinese cities. We employed multivariable Cox regression to assess time-to-event outcomes, smooth curve fitting for trend analysis, and inflection point analysis to determine critical thresholds. Subgroup analyses were performed to explore interactions. Mediation analysis was conducted to clarify the mechanisms linking prediabetes with health outcomes. In the analysis of 24,884 individuals, it was observed that 49.08% of the prediabetic subjects experienced normoglycemic conversion during a follow-up period spanning 73,517.66 person-years. Following full adjustment, the Cre/BW ratio was positively associated with normoglycemic conversion among prediabetic individuals (HR 1.42, 95% CI 1.30-1.55). Multivariate smooth spline analysis revealed a nonlinear relationship between the Cre/BW ratio and glucose status conversion (P for nonlinearity <
0.05), with the curves leveling off when the Cre/BW ratio (×100) reached 1.34. Subgroup analysis and additional sensitivity analyses confirmed that the results between the Cre/BW ratio and glucose status conversion were robust. Additionally, the De Ritis ratio was found to explain 50% of the association between the Cre/BW ratio and the prediabetes-to-normoglycemia transition. A higher Cre/BW ratio was associated with a better chance of controlling blood glucose levels in prediabetic individuals, with the De Ritis ratio playing a key mediating role.