Saliva is a bodily fluid secreted by the salivary glands. Due to its easy accessibility and non-invasive sampling, it has increasingly been studied in the scientific investigations. Saliva contains opiorphin, a pentapeptide that has been found to have analgesic effects. This effect is based on its dual inhibitory action on neutral endopeptidase and aminopeptidase N, which are involved in the catabolism of enkephalins. Unlike opioid analgesics, it does not cause addiction or tolerance. Furthermore, it has been shown to have antidepressant effects and to affect intestinal peristalsis, blood pressure, and the regulation of penile smooth muscle tone. In determining its concentration, two standardized methods, ELISA and LC-MS/MS, are most commonly used. In addition to its physiological effects, changes in opiorphin concentration have been observed in certain chronic diseases and conditions of the oral cavity. Its concentrations have been investigated in temporomandibular disorders, burning mouth syndrome, symptomatic irreversible pulpitis, symptomatic apical periodontitis, and oral ulcers of various aetiology. Most studies have described increased opiorphin concentrations in the examined diseases and conditions, particularly in cases with more pronounced pain symptoms. Current findings suggests that opiorphin has great potential as a diagnostic and therapeutic tool. However, only a limited number of studies have been conducted since its discovery, therefore, further research is needed to confirm these findings on a larger sample size and to explore additional functions and therapeutic possibilities of opiorphin.