Due to climate change, rapid warming and its further intensification over different parts of the globe have been recently reported. This has a direct impact on human health, agriculture, water availability, power generation, various ecosystems, and socioeconomic conditions of the exposed population. The current study thus investigates the frequency and duration of heatwaves, human discomfort, and exposure of the human population to these extremes using the high-resolution regional climate model experiments under two Representative Concentration Pathways (RCP2.6, RCP8.5) over India. We find that more than 90% of India will be exposed to uncomfortable warm nights by the end of the 21st century with the highest rise over western India, Madhya Pradesh (MP), Uttar Pradesh (UP), Punjab, and the Haryana region. States like Odisha, Chhattisgarh, eastern parts of MP and UP, and some parts of J&K will be the worst hit by the intense and frequent heatwaves and human discomfort followed by the densely populated Indo-Gangetic plains under RCP8.5. Strict enforcement of the stringent policies on stabilization of population growth, improvement of local adaptive capacities, and economic status of the vulnerable population along with enforcing effective measures to curb greenhouse gas emissions are important to reduce human exposure to future heat stress. We demonstrate that a proper mitigation-based development (RCP2.6) instead of a business-as-usual scenario (RCP8.5) may help to reduce 50–200 heatwave days, 3–10 heatwave spells, and 10–35% warm nights over the Indian region. Consequently, this can avoid the exposure of 135–143 million population to severe discomfort due to extreme heat conditions by the end of the 21st century.