Abnormal dislocation of cone opsin protein affects the sensitivity function of photoreceptors and results in depressed central vision. Nutraceutical therapy is needed to restore the residual function of photoreceptors. Crocin is a natural substance for retinal health. However, its effect on the restoration of functional vision and its underlying mechanisms have not been fully studied. This study analyzed the restorative effect of crocin on residual functional vision in vivo in a mouse model. High-energy light-evoked photoreceptor dysfunction was confirmed by M opsin dislocation in the retina accompanied by a loss of functional vision. Crocin treatment significantly increased brain-derived neurotrophic factor (BDNF) protein in retinas, thus contributing to the re-localization of the M opsin protein, restoration of the visual acuity (VA), and high spatial frequency-characterized visual contrast sensitivity function (VCSF). In contrast, such effects were significantly reversed after the washout period. Additionally, the restorative effect of crocin on functional vision and M opsin re-localization can be reversed and blocked by synchronous injection of a tropomyosin receptor kinase B (TrkB) receptor antagonist (ANA-12). This study demonstrated the major functional vision-rescuing or restoring effect of crocin in vivo by modulating M opsin location plasticity and increasing the capacity of the residual photoreceptor function through the BDNF–TrkB receptor pathway.