The clinical performance of dental composite restoration and its overall success are the result of physical, mechanical, and biological properties of the filling materials. The present study aimed to evaluate surface roughness, flexural properties, and cytotoxicity of two nanohybrids, namely, MI Gracefil and Herculite Ultra, and one nanoceramic dental resin composite DiamondLite. The surface roughness was assessed in two different grinding conditions. Flexural properties were measured by, the three-point bending test and the specimens’ fractured surface was analyzed by scanning electron microscopy. Weibull analysis was performed on the flexural strength data to determine the composites’ reliability. The cytotoxicity test was conducted on MC3T3-E1 cells by the MTS assay. The results showed that grinding conditions had a significant effect on all nanocomposites' surface roughness ( p < .05). Herculite Ultra had a significantly higher flexural strength (125.8 MPa) and flexural modulus (9.8 GPa) as compared to other two nanocomposites ( p < .05). Further, cytotoxicity results indicated that DiamondLite had the lowest cell viability during the incubation period ( p < .05). The current study, therefore, concluded that the evaluated nanocomposites showed satisfactory surface roughness. Herculite Ultra flexural properties and Weibull modulus results make it a reliable choice for direct restorations. The cell viability results also showed that all three nanocomposites had moderate cytotoxicity, making them acceptable for direct application in the mouth.