Background: Conventional learning through lecturing decreases students’ involvement whereas students’ active participation in class promises more benefits. The development of active learning method can help hone students’ soft skills in thinking critically and systematically. This study aimed to identify the influence of self-regulated learning (SRL) on students’ active participation and learning outcome in the Nervous System Pharmacotherapy subject. Students’ response towards the self-regulated learning method would also be described. The study used a quasi-experimental quantitative approach with a non-equivalent control group design involving four classes of fifth-semester pharmacy students during December 2016. Students were divided into 2 control groups (155 students) and 2 intervention groups (124 students), which were then divided into 1 case group involving an international lecturer and SRL application as well as 1 case group involving an internal lecturer and SRL application. Learning outcome was assessed based on the average final score and pass rate of all students compared to the average final score of last year’s students, while the active participation was graded from their ability to do a presentation. To identify students’ response towards the learning process using SRL, a questionnaire adopted from other studies was utilized. There was an improvement in the average final score of all students of 2016/2017 as much as 70.94 compared to the average final score of all students of 2015/2016, which was 67.8. The evaluation on students’ active participation showed a relatively satisfactory result with 7.25 average score in Case 1 Group and Case 2 Group and 6.99 in the Control Group. The students also indicated positive responses to the implementation of SRL method, reaching 81.3%. The implementation of self-regulated learning could improve students’ active participation and learning outcome in Nervous System Pharmacotherapy.