Introduction: Limited research exists on effective pre-departure training (PDT) for interprofessional healthcare disciplines participating in international service-learning (ISL), particularly to resource-limited settings. Method: A convenience sample of 21 physical and occupational therapy students and clinicians who participated in four 1-hour PDT sessions were included in this mixed-methods study. Training consisted of informative, reflective, and simulation experiences to enhance self-awareness, teambuilding, cultural knowledge, and in support of trip preparations. Training session debriefings were transcribed and coded. The Cross-Cultural Adaptability Inventory (CCAI™) was administered pre-training and post-experience. Results: Qualitative data showed emerging themes around collaboration, mentorship, empowerment, opportunity, preparedness, self-awareness, and confidence. Quantitative analysis of CCAI™ data revealed significant median differences between a) all participants' CCAI™ scores for perceptual acuity pre = 49.29 and post = 51.38 (p = 0.018); as well as b) students CCAI™ scores of perceptual acuity pre = 49.80, post = 51.46 (p = 0.040); and c) clinicians CCAI™ personal autonomy scores pre = 31.00 and post = 33.16 (p = 0.042). Discussion: Participants demonstrated improved ability to perceive the needs of this novel culturally novel community and respond appropriately to community members and across healthcare disciplines. Conclusion: Pre-departure training prepares healthcare providers for international service, enhances emotional intelligence, improves interprofessional collaboration, and promotes more continuously sustainable services.