Background Pre-diabetes (PD) contributes importantly to the disease burden worldwide and is a precursor to stroke, cardiovascular diseases, as well as type-2 diabetes mellitus. Objective In this project, the efficacy of individualized homeopathic medicines (IHMs) was explored against placebos in the treatment of PD. Methods A 6-month, double-blind, randomized, placebo-controlled trial was conducted at the outpatient departments of a homeopathic medical college and hospital in India. Sixty participants with PD were randomized to receive either IHMs (n = 30) or identical-looking placebos (n = 30). Concomitant care measures were advised to both groups of participants in terms of dietary advice, yoga, meditation and exercise. The primary outcome measures were fasting blood sugar (FBS) and the oral glucose tolerance test (OGTT); the secondary outcome was the Diabetes Symptom Checklist-Revised (DSC-R) score. All the outcomes were measured at baseline and after 3 and 6 months of treatment. Inter-group differences and effect sizes (Cohen’s d) were calculated using two-way repeated measures analysis of variance models after adjusting baseline differences using analysis of co-variance on the intention-to-treat data. Results Between-group differences for FBS were statistically significant, favoring IHMs against placebos (F 1,58 = 7.798, p = 0.007), but not for OGTT (F 1,58 = 1.691, p = 0.199). The secondary outcome, DSC-R total score, favoring IHMs significantly compared with placebos (F 1,58 = 15.752, p < 0.001). Calcarea Carbonicum, Thuja occidentalis and Sulphur were the most frequently prescribed medicines. No harm or serious adverse events were recorded from either of the participant groups. Conclusion IHMs produced significantly better results than placebos in FBS and in DSC-R scores but not in OGTT. Independent replications with larger sample sizes are warranted to substantiate the findings.