This study investigated the relationship between sex hormones, post-operative pain, and opioid use following third molar extraction. Eighty-five healthy adults (48 women, 37 men; ages 18–37) provided baseline blood samples, which were analyzed for hormone levels using ELISA. Pain intensity was recorded on a 0–10 numeric scale during a 4-hour inpatient period. Patients received either ibuprofen or a placebo pill in a randomized, double-blind design once their pain reached a score of 4/10 or higher. Post-discharge, patients managed pain with scheduled ibuprofen and acetaminophen, and oxycodone was provided for breakthrough pain. While no statistically significant associations were identified between hormone levels and pain scores, women were more likely than men to use opioids, and preliminary trends suggested oral contraceptive users required fewer opioids than non-users. Hormone levels aligned with expected physiological patterns, confirming the reliability of the data and hormone assays. These findings highlight potential modulatory effects of sex hormones on pain perception and opioid use, warranting further investigation with larger cohorts.