Fluoride is a naturally occurring element found in soil, rocks, and groundwater, and its controlled use in drinking water is a well-established public health measure to prevent dental caries. However, growing evidence indicates that excessive fluoride exposure, particularly during critical periods of neurodevelopment, may exert neurotoxic effects. This systematic review evaluates current evidence on fluoride-induced neurotoxicity from in vitro, in vivo, and epidemiological studies. The findings reveal that fluoride exposure can induce oxidative stress, mitochondrial dysfunction, apoptosis, and impaired autophagy, leading to neuronal damage, synaptic deficits, and cognitive impairments. Protective mechanisms involving sirtuin proteins (SIRT1 and SIRT3) have been identified as potential modulators of fluoride-induced neurotoxicity. These results underscore the importance of monitoring fluoride exposure levels, particularly during early brain development, and lay the groundwork for future research on underlying mechanisms and preventive strategies.