In this generation, many factors affect learning particularly in Science. Thus, this study aimed to enhance students’ Science process skills through self-directed learning guide. It also attempted to determine significant difference between the result of pre-assessment and post-assessment tests of students’ performance in the Science process skills test. Using a descriptive-developmental method of research, it involved the 70 purposively selected Accountancy, Business, and Management (ABM) Grade 11 students in San Jose National High School, San Pablo City during the Academic Year 2017- 2018. Survey questionnaire and science process skills test were utilized to gather the data and these were analyzed using frequencies, percent counts, and Spearman’s rho. Results revealed that most of the respondents perceived the attitude in Science as highly positive and they were interested in Science with visual and kinesthetic learning styles. In terms of the perceived level of effectiveness of the self-directed learning guide in Physical Science, learning experience, learning outcome, and userfriendliness, the respondents were all perceived to be very much effective while in effectiveness and efficiency, were perceived to be highly evident. The pre-assessment and post-assessment tests of the students were significantly different which implies that students’ science process skills were improved due to the designed learning guide.