The main focus of the present research was to examine the appropriateness of groundwater resources for drinking purposes in the Bilate River Basin of Southern Main Ethiopian Rift, Ethiopia. The groundwater quality index (GWQI), fluoride pollution index (FPI), and human health risk were used to examine the human health risk factors associated with the intake of high fluoride groundwater. For this purpose, 29 groundwater samples were collected from the existing wells and were analyzed for various physicochemical parameters. The dominant cation was Na+, followed by Ca2+, Mg2+, and K+. The dominant anion was HCO3-, followed by Cl-, SO42-, and F-. The Gibbs plot shows that rock-water interactions are the dominant factor controlling the groundwater chemistry. By using the GWQI, the quality of groundwater samples was 31% excellent, 21% good, 31% poor, and 17% very poor. The fluoride concentration in groundwater ranges from 0.2 to 5.60 mg/L (mean, 2.10 mg/L). 59% (i.e., 17 wells) of the groundwater samples were not suitable for drinking, because they surpassed the drinking water quality limit of 1.5 mg/L. The remaining 41% (i.e., 12 wells) of the samples were suitable for drinking. The FPI indicates that 51.72% of the wells were highly polluted by fluoride. The noncarcinogenic health risk varies from 0.75 to 8.44 for children (83%), 0.34-3.84 for women (62%), and 0.27-3.01 for men (52%), which indicates that children are at higher health risk than women and men due to the physiological condition and the rates of ingestion.