<p>Heme oxygenase-1 (HO-1/Hmox1) has emerged as a critical regulator of oxidative stress, inflammation, and cellular protection since its discovery in 1968. Initially characterized for its role in heme degradation, HO-1 is now widely investigated for its therapeutic potential in cardiovascular diseases, neurodegeneration, cancer, and infectious conditions such as COVID-19. Globally, research efforts have been concentrated in the United States, China, and South Korea; however, India has increasingly contributed to the field through genetic studies, translational research, and exploration of natural HO-1 modulators with therapeutic relevance. Using Web of Science Core Collection data, this scientometric analysis highlights evolving research trends, identifies key thematic clusters, and maps India’s emerging role in HO-1 research. Co-occurrence and co-citation analyses reveal two dominant focuses: gene regulation and cellular mechanisms involving apoptosis, inflammation, and cancer, with Indian studies providing unique insights into population-specific genetic polymorphisms and disease susceptibility. Although HO-1 holds considerable clinical promise, challenges remain due to its complex dual role—offering cytoprotection but potentially promoting tumor progression. Furthermore, HO-1 deficiency (HMOX1D), while rare, has serious clinical implications that may be underdiagnosed in India. Future research should emphasize tissue-specific studies, advanced genetic models, and rigorous clinical trials to translate findings effectively within the Indian healthcare context. This study underscores the value of scientometric approaches in uncovering research patterns, guiding collaborative efforts, and shaping targeted exploration of HO-1’s multifaceted biological roles and therapeutic potential, particularly from an Indian perspective.</p>