: Up to 25-70% of proton-pump inhibitor (PPI) prescriptions worldwide lack an evidence-based indication, exposing patients to avoidable adverse events and unnecessary costs. Community pharmacists (CPs) are well-equipped to curb the misuse of PPIs. This study aimed to quantify CPs' knowledge, attitudes, and practices (KAPs) regarding PPIs in two high-use Middle-Eastern markets and determine how demographic and professional factors influence guideline-adherent PPI use. Bridging this gap is crucial to ensure pharmacists can promote rational PPI use, provide accurate patient counseling, and reduce the likelihood of adverse outcomes. : An online cross-sectional survey was undertaken between May 2024 and July 2024 to investigate the KAPs of CPs in Egypt and Iraq toward PPI use. The self-developed thirty-item questionnaire (17 knowledge, 11 attitude, and 6 practice items) was piloted with 30 CPs. A sample size of 385 CPs was required based on an estimated 93,000 community pharmacists in Egypt and 22,120 in Iraq; however, to improve statistical power, we aimed to include >500 CPs. : A total of 527 CPs from Egypt and Iraq completed the survey. The total median scores for knowledge, attitude, and practice were 11 out of 17 (IQR: 9-16), 9 out of 11 (IQR: 6-12), and 5 out of 6 (IQR: 3-8), respectively. CPs with >20 years of experience and those who relied on clinical guidelines as a primary information source demonstrated a median knowledge score significantly higher than those with fewer years of experience ( = 0.001 and 0.028, respectively). There was a significant positive association between knowledge and attitude, knowledge and practice, and attitude and practice scores (coefficients: 0.832, 0.701, and 0.445, respectively). : Although their attitudes and practices regarding PPI use were satisfactory, the knowledge of CPs about the judicious use of PPIs requires improvement. Thus, a call for action targeting their tailored education and training is necessary to address these knowledge gaps regarding PPIs identified, including PPI adverse-effect profiles, evidence-based indications, and deprescribing criteria, and to foster informed medication attitudes and practices. Such education and training can reinforce guideline adherence, enhance patient counseling skills, and ultimately reduce inappropriate PPI use.