Sciatica is a debilitating condition in which the patients experience pain in the distribution of the sciatic nerve or associated lumbosacral nerve root. Homeopathy is claimed to be beneficial for sciatica pain; still, systematic research evidence remains compromised. To objective of the trial was to examine the efficacy of individualized homeopathic medicines (IHMs) against identical-looking placebos in the treatment of sciatica pain. A double-blind, randomized (1:1), two parallel arms, placebo-controlled trial was conducted at Mahesh Bhattacharyya Homoeopathic Medical College and Hospital, Howrah, West Bengal, India. Participants were randomized equally to receive either verum (n = 30; IHMs plus concomitant care) or control (n = 30; placebos plus concomitant care). Primary outcome measures were Sciatica Bothersome Index (SBI) and Sciatica Frequency Index (SFI) scores; and secondary outcomes were Roland Morris Pain and Disability Questionnaire (RMPDQ), Short Form McGill Pain Questionnaire (SF-MPQ), and Oswestry Low Back Pain Questionnaire (OLBPQ) scores; all of them were measured at baseline, and every month, up to 3 months. Intention-to-treat sample (n = 60) was analyzed. Group differences were examined by two-way (split-half) repeated measure analysis of variance, primarily taking into account all the estimates measured at monthly intervals, and secondarily, by unpaired t-tests comparing the estimates obtained individually every month. The level of significance was set at P less than 0.025 and 0.05 two-tailed for the primary and secondary outcomes respectively. Group differences could not achieve significance in SBI (P = 0.044), SFI (P = 0.080), and RMPDQ scores (P = 0.134); but were significant for SF-MPQ (P = 0.007) and OLBPQ (P = 0.036). Gnaphalium polycephalum (n = 6; 10%) was the most frequently prescribed medicine. No harm, serious adverse events, and intercurrent illnesses were recorded in either of the groups. Although the group differences in the primary outcomes were not large enough to be statistically significant favoring homeopathy against placebos, still, promising effects were detected in the secondary outcomes and the secondary analyses. Independent replications are warranted to confirm the findings.