To evaluate nanohardness of normal and fluorosed enamel in teeth restored with Cention N (CN), Equia forte (EF), glass ionomer cement (GIC), and resin composite using the nanoindentation test. Eighty freshly extracted human premolars were selected. Standardized cavities were prepared on the buccal surface of normal (40) and fluorosed (40) teeth. Based on the type of the restorative material, the teeth were subgrouped into (n = 10): CN, EF, Type VIII GIC, and Tetric N-Ceram (TNC). The teeth were subjected to pH cycle (progressive caries test), which consisted of alternative demineralization (18 hours) and remineralization with artificial saliva (6 hours) for 3 consecutive days. Surface nanohardness was determined using a nanoindenter at distances of 100, 200, and 300 μm from the restoration-tooth margin. A polarized light Microscope was used to correlate the effect of remineralization on the enamel. Data were analyzed by one-way ANOVA with the Scheffe's post hoc and independent t-test. Nanohardness values of the fluorosed/normal enamel adjacent to various materials in descending order were as follows: EF 3.67/2.95 GPa, GIC 3.33/3.15 GPa, CN 3.13/3.23 GPa, and TNC 1.17/1.82 GPa, respectively. Statistically significant differences were found among various materials in both types of the enamel (p < 0.05). Based on the nanohardness test, EF can be a better choice for restoration in fluorosed teeth, followed by CN and GIC; GIC was better in normal enamel; however, this was not significant compared to CN and EF. Tetric N-Ceram composite resin had least influence on increasing the nanohardness of the adjacent enamel. The surface nanohardness of normal and fluorosed enamel can be influenced by the type of restorative material used. The results of present study deserve clinician's attention while selecting restorative materials especially in dental fluorosis.