Background: Rabies is a neglected zoonotic disease. It is transmitted through the bite of a rabid animal and dog bites are responsible for around 95% of human cases. The disease is almost always fatal after the onset of symptoms. It is an endemic and major public health problem in India with one-third of the global deaths reported from this country. Protocol: This systematic review aims to estimate the epidemiological, humanistic and economic burden of dog-mediated rabies in India. Initially the existence of controlled descriptors in MeSH terms (such as 'Epidemiology', 'Rabies', 'Cost', 'Dog bite', 'Quality of Life', 'India' etc), and their synonyms (key words) was identified in MEDLINE, and were later combined with Boolean operators 'AND' and 'OR' to develop a detailed search strategy. Two independent reviewers will screen the titles and abstracts and select the studies as per the inclusion criteria. The selected studies will be assessed for their quality and risk of bias. Data will be extracted using standardized data extraction tools and will be synthesized for analysis. Disagreements that arise between the reviewers will be resolved through discussion, or with a third reviewer. Discussion: This systematic review will be performed to critically examine relevant literature and report the epidemiological, humanistic and economic burden of dog-mediated rabies in Indian context. The findings will help in estimation of burden of the disease in India and expected to contribute in policy making and planning of the program and interventions in the country. Protocol registration: PROSPERO ID: CRD4202021326.