Abstract Background Autism spectrum disorder (ASD) is an umbrella term used to describe a constellation of early-appearing social communication deficits and repetitive sensory-motor behaviours. There is a dramatic increase in prevalence of ASD in the past few decades. Autism is a potentially lifelong impairing disorder usually managed with complementary therapies, symptomatic behavioural, sensory integration therapies and medical treatments. As there are currently no specific medicines that can address core disabilities of ASD, there is a desperate need to explore new interventions in ASD. Objectives The aim of this study is to assess the effectiveness of homoeopathic medicines in the usual care setting, i.e. regular OPD, for the management of ASD using Autism Treatment Evaluation Checklist (ATEC). Materials and Methods The present study is a case series analysis of 20 cases diagnosed as ASD and evaluated with ATEC in the outpatient unit of Department of Psychiatry, National Homoeopathy Research Institute in Mental Health. Individualised homoeopathic medicines were prescribed based on classical homoeopathic principles. Wilcoxon signed-rank test was used to compare ATEC scores at baseline to end of 12 months. Results The median baseline ATEC score of 110.0 (116.0–94.5) reduced to 33.5 (61.75–25.0) at p < 0.001, with an effect size of 0.88. There was statistically significant difference in all domains of speech language communication, sociability, sensory/cognitive awareness and health/physical/behaviour when compared from baseline to end of 12 months. Calcarea carbonica, Calcarea phosphorica, Carcinosinum, Mercurius solubilis, Natrum muriaticum, Silicea, Theridion, Tuberculinum, Zincum metallicum etc. were commonly indicated homoeopathic medicines. Conclusion Individualised Homoeopathic medicines are effective in the management of ASD. Well planned, methodically rigorous research is warranted to corroborate the evidence.