Mental health is crucial to overall well-being. Despite an increase in mental disorders over the past few decades, public awareness remains slow-growing, and stigmatization towards psychotropic medications persists. Therefore, this study aimed to identify knowledge and perceptions of psychotropic drugs among the general population in the Makkah Region, Saudi Arabia. A questionnaire-based cross-sectional study was conducted among adults aged 18 years old and older, living in the Makkah Region, Saudi Arabia, from 1 January to 30 April 2024. Descriptive statistics were used to describe participants' characteristics, and categorical variables were reported as frequencies and percentages. A Chi-square test was used to examine the relationships between variables. A total of 717 participants were involved in the study: (52%) were from Jeddah, (25.9%) were from Taif, and (22%) were from Makkah. The mean age was 33.9 years, and 67.1% were females. Among the participants, (20.8%) had experienced a psychiatric illness, (41.7%) had a member of the family who suffered from a psychiatric illness, (39.5%) had a family member who used a psychiatric drug, and only 25 (7%) had a child suffering from a psychiatric illness. Specifically, 20.8% of those with a psychiatric illness demonstrated good knowledge (P=0.001), 16.1% of those with a family history of psychiatric illness had good knowledge (P=0.007), 16.3% with family use of psychiatric drugs had good knowledge (P=0.006), and 24.5% of those who used psychiatric drugs had high knowledge (P=0.001). Overall, (40.6%) of participants had a low level of knowledge and perception about psychotropic drugs, (47.8%) had a moderate knowledge and perception level, and only (11.6%) had high knowledge and perception. Psychological well-being is crucial for health, but misconceptions persist, acting as barriers that impede people from seeking and accepting necessary psychiatric care. The findings highlight the need for targeted public education and healthcare professional training to improve Confirmed understanding and reduce stigma around psychotropic drugs in Saudi Arabia. A multifaceted approach involving policy development, community outreach, and ongoing research is essential for enhancing mental health outcomes and treatment accessibility.