The international opioid crisis highlights the important role of pharmacists in prevention, using their availability and drug knowledge to prevent abuse. In this study, the knowledge, attitudes, and practices of Mangalore pharmacists towards preventing opioid abuse were assessed. From February to March 2025, a cross-sectional survey was done among 203 pharmacists aged 18-46 years in Mangalore using a pre-tested structured questionnaire. Data were analyzed using the Chi-square test, and thematic analysis of qualitative feedback. Pharmacists showed high knowledge, with 93.6% identifying opioids' mechanism as binding to CNS receptors correctly, 78.8% identifying naloxone's role in reversing overdose, and 70.0% knowing prescription drug monitoring programs' usefulness. Attitudes were optimistic, with 92.6% considering patient education a primary responsibility, 92.1% identifying multiple visits to the pharmacy as misuse, and 93.1% supporting medication-assisted treatment. The practice was active, with 93.1% checking prescription drug monitoring programs for suspected misuse and 69.0% advising take-back programs, but 43.8% associated early refills with misuse. Mangalore pharmacists show strong knowledge, attitudes, and practice against opioid abuse, being very strong in education and medication-assisted treatment support but having voids in misuse detection (for example, recognition of early refill) and naloxone confidence. Stronger training, better prescription drug monitoring program access, and policy adjustments can enhance their role in India's opioid strategy. Pharmacists are presented as front-line champions of opioid misuse prevention in this study, with implications for localized harm reduction.