The main objective of the present study is to perform risk assessment of groundwater contaminated by nitrate (NO3−) and evaluate the suitability of groundwater for domestic purposes in the Palani region of South India. Thirty groundwater samples were collected in the study area. Various groundwater quality analysis parameters such as the pH, electrical conductivity, total dissolved solids, total hardness, major cations (Ca2+, Mg2+, Na+, and K+), and major anions (Cl−, SO42−, F−, CO32−, and HCO3−) were adopted in this study to evaluate the drinking water suitability according to 2011 World Health Organization (WHO) standards. Piper and Gibbs’s diagrams for the tested groundwater indicated that, due to the influence of rock–water interactions, evaporation, and reverse ion exchange, the chemical composition of groundwater varied. According to water quality index (WQI) mapping results, 46.67% of the sample locations was identified as contaminated zones via GIS spatial analysis. Multivariate statistical analysis methods, such as principal component analysis, cluster analysis, and the Pearson correlation matrix, were applied to better understand the relationship between water quality parameters. The results demonstrated that 40% of the samples could be identified as highly affected zones in the study region due to a high nitrate concentration. The noncarcinogenic health risks among men, women, and children reached 40, 50, and 53%, respectively. The results illustrated that children and women occurred at a higher risk than did men in the study region. The major sources of contamination included discharge from households, uncovered septic tanks, leachate from waste dump sites, and excess utilization of fertilizers in the agricultural sector. Furthermore, using the nitrate health hazard integrated method with the conventional indexing approach ensures that groundwater reliability can be guaranteed, contamination can be explored, and appropriate remedial measures can be implemented.