Living in different aquatic ecosystems, otters play a vital role in maintaining aquatic species assemblages, particularly fish communities. Thus their wellbeing indicates the health of wetland ecosystems. Smooth-coated Otter Lutrogale perspicillata, a piscivorous mustelid, is widely distributed across Asia. Its population is declining due to habitat transformation, pollution and hunting. This study aimed to understand the ecological requirements of the species by assessing its distribution and its determinants, population and diet composition along the Cauvery River in Hosur and Dharmapuri Forest Divisions. Through monthly extensive surveys between December 2010 and February 2011, covering 62.5 km of Cauvery from the Karnataka border to Palar River junction, this study identified and mapped a 31 km stretch from Dubguli (Yellolapatti) to Biligundlu (Musulumaduvu) as an otter distribution area. Comparison of ecological parameters including bank type, water depth, river width, human disturbance, vegetation cover and water current with the distribution pattern of otters across 125 blocks revealed that water depth and vegetation cover influenced otter distribution positively, while human disturbance had negative influence (these three variables explained 54% of variation in otter distribution). Based on direct sightings, seven different groups consisting of 36 individuals were estimated as the minimum population. The mean group size was 3.8 ± 0.16 (range: 2–7) individuals. Twenty-one otter spraints were analyzed to determine diet composition, revealing that otters feed on insects, molluscs, crabs, fish, frogs, reptiles and birds. Fish constituted the bulk of otter diets. Conservation measures like reducing anthropogenic pressures (e.g., fishing, cattle pens, tourism), increasing awareness of sustainable fishing to stakeholders, and instituting long-term monitoring programs are suggested for the long-term conservation of otters in the study area.