Diseases like viral keratitis can harm corneal nerves, which are necessary for maintaining the health and functionality of the cornea. Recent research has shown that corneal nerve pathology affects the infected eye as well as the contralateral one, and that aberrant changes in sympathetic nerves can be seen, with the exception of sensory nerves that correspond to corneal sensation. However, apart from in vivo confocal microscopy and corneal sensation, there have been no additional prognostic indicators that allow clinicians to assess the severity of corneal nerve damage. While multiple functions of corneal nerves are mediated by neuropeptides, substance P, the first topical neuropeptide used in ocular clinical practice, was proved to regulate the process of viral infections, and it is involved in bilateral corneal pathologies through pro-inflammatory and neurotrophic functions in viral keratitis, so it may be used as a diagnostic biomarker or a therapeutic target. Therefore, this review summarized the changes and roles of corneal nerves as well as substance P in viral keratitis, which may serve as a reference for further study into associated mechanisms and clinical applications.