Student encountered challenges in performing guided inquiry learning (GIL) activities are a minority literature in science education, but may provide valuable inputs to developing science process skills vital to scientific literacy. This study determined the challenges and difficulties by science-oriented students in performing GIL activities in biology. Cluster sampling determined the participants in the pre-survey (69 grade 8 students) and the actual investigation (30 grade 8 students). A validated survey questionnaire pre-identified the six major difficulties of the students. Validated student and expert questionnaires assessed the level of difficulty in each of the task on the six pre-identified challenges. Results show that science-oriented students and the experts assessed the following with a fair difficulty level: background knowledge; performance of laboratory procedure; managing extended activities; designing an experiment; and writing a laboratory report. The same group assessed the task -- data analysis to be "difficult." The upper (high average to superior IQ) group and lower (average to above average) groups of science oriented students provided a non-significant difference in their difficulty assessment of all the tasks. However, replicating the study to include low cognition students from non-science oriented schools may provide a wider perspective of these student-encountered difficulties and challenges in GIL.