Fluoride exposure results in several pathophysiological conditions associated with neurodegenerative changes, these include anxiety, memory loss, disturbance in cognition and motor learning, etc. Thus, the objective of the present study was to examine the protective effect of antioxidants Resveratrol (Resv) and Curcumin (Cur) on chronic NaF (Sodium Fluoride,120 ppm for 30 days) induced anxiety behavior and retarded exploratory motor activities, by using elevated plus maze (EPM), and open field test (OFT), as a behavioral paradigm. Effects on intracellular calcium concentration and cell viability were also studied in vitro. Histochemistry was done to assess the effect of treatments on Acetylcholine neurotransmitter. The data indicated that NaF-induced anxiety-like behavior was evident from decreased exploration activity in OFT with increased anxiety levels in EPM, whereas on providing the Resv or Cur (30mg/kg. body weight, for 30 days) these behavioral changes and the fibrous staining of acetylcholine neurons of brain subregions i.e. CA1, CA3, Perirhinal, and Dorsolateral entorhinal cortex, were restored. The beneficial effect of phytochemicals to improve neuronal connections was validated by performing immunohistochemical staining of doublecortin (DCX) and neuronal nuclei (NeuN), to evaluate neuronal migration and synaptic integration in the mentioned subregions of mice brain. The result suggests reparative potential of Resv and Cur, showing higher neuro-modulatory potential by ameliorating AChE to relieve stress and restoring synaptic plasticity in the cortical-hippocampal system offering great potential as a novel preventive therapeutic agent for anxiety and ameliorating exploratory motor activity.