Background: Several studies assessed the level of knowledge and general public behavior on human immunodeficiency virus/acquired immuno-deficiency syndrome (HIV/AIDS) in India. However, comprehensive scrutiny of literature is essential for any decision-making process. Our objective was to perform a systematic review and meta-analysis to examine the level of knowledge and attitude towards HIV/AIDS in India. Methods: A systematic search using Medical Subject Headings (MeSH) and free terms was conducted in PubMed/Medline, Scopus, Embase, and Google Scholar databases to investigate the level of knowledge and attitude of HIV/AIDS in India population. Cross-sectional studies published in English from January 2010 to November 2020 were included. The identified articles were screened in multiple levels of title, abstract and full-text and final studies that met the inclusion criteria were retrieved and included in the study. The methodological quality was assessed using the Joanna Briggs Institute’s checklist for cross-sectional studies. Estimates with corresponding 95% confidence intervals (CIs) for each domain were pooled to examine the level of knowledge and attitude towards HIV/AIDS in India. Results: A total of 47 studies (n= 307 501) were identified, and 43 studies were included in the meta-analysis. The overall level of knowledge about HIV/AIDS was 75% (95% CI: 69-80%; I2 = 99.8%), and a higher level of knowledge was observed among female sex workers (FSWs) 89% (95% CI: 77-100%, I2 = 99.5%) than students (77%, 95% CI: 67-87%, I2 = 99.6%) and the general population (70%, 95% CI: 62-79%, I2 = 99.2%), respectively. However, HIV/AIDS attitude was suboptimal (60%, 95% CI: 51-69%, I2 = 99.2%). Students (58%, 95% CI: 38-77%, I2 = 99.7%), people living with HIV/AIDS (57%, 95% CI: 44-71%, I2 = 92.7%), the general population (71%, 95% CI: 62-80%, I2 = 94.5%), and healthcare workers (HCWs) (74%, 95% CI: 63-84%, I2 = 0.0%) had a positive attitude towards HIV/AIDS. The methodological quality of included studies was "moderate" according to Joanna Briggs Institute’s checklist. Funnel plots are asymmetry and the Egger’s regression test and Begg’s rank test identified risk of publication bias. Conclusion: The level of knowledge was 75%, and 40% had a negative attitude. This information would help formulate appropriate policies by various departments, ministries and educational institutions to incorporate in their training, capacity building and advocacy programs. Improving the knowledge and changing the attitudes among the Indian population remains crucial for the success of India’s HIV/AIDS response.