Human beings' concern for hygiene and restoring health to the body in various situations, especially when traveling, has been an ever-present issue. Therefore, the current research is based on this question: What was the response to the hygienic and health needs of travelers in Safavid Iran? The findings of the present study, based on a descriptive-analytical method, show that travel in the Safavid era, with various religious, military, and commercial goals and motives, was primarily done on land (on foot and horseback), and by sea. Under hygiene protection measures and various treatment methods, the behavioral approach to responding to the traveler's hygiene and health needs is presented under the intellectual atmosphere and the humor medicine system (four temperaments). The occurrence of various physical and mental challenges for the traveler along the way was the result of moving while traveling. Therefore, gaining the necessary knowledge, taking measures, and making changes in habits and patterns of behavior before traveling was necessary to prepare the body. Adhering to six core principles of maintaining hygiene safeguarded the health of the traveler's body during travel. In proportion to the duration of the travel and the two important variables of heat and cold, there was the possibility of catching various diseases and facing harmful conditions such as thirst, hunger, fatigue, heatstroke, frostbite, scalding, and injuries. Different treatments have been provided by physicians to solve all kinds of conditions and complications, depending on the situation and temperament of the person.