Genetics is considered as one of the topics in science that students have difficulty and trouble in understanding. This study used study guide as an intervention tool to address the difficulties of students in learning genetics concepts. The main purpose of this study was to determine the perceptions of students on the effectiveness of study guide in enhancing motivation and learning in genetics lessons.The study used descriptive action research design. The development and evaluation of the study guide focused on the ADDIE Model. The respondents of the study were 75 students of Gingoog City Comprehensive National High School (SY 2015-2016).The study guide is a double-sided A4 size hard copy colored sheets that contains genetics concepts. The concepts were presented in the form of diagram and pictures. The study guide was handed out to students at the beginning of the 4th quarter where genetics lessons are dealt. The respondents answered the survey questionnaire at the end of the lessons. The results of the present study revealed that the students strongly agree that the study guide presented figures/pictures which are colourful and attractive that makes it interesting and provided adequate and comprehensive information. Majority of the students perceived that the study guide helped them when undertaking tests or exam followed by tutorials, reports and assignments. Moreover, students strongly perceived that the use of the study guide is very effective as supplemental tool in learning genetics concepts. The study guide exhibits good features that motivated students to read, learn and understand genetics lessons.