This study investigated the effect of mentoring and gender on the achievement of low-performing students in Biology. Its main purpose was to measure the response rate of each gender to mentoring approach of science teaching. It is believed that this will assist in developing individual potentials to becoming better science learners. The study employed the non-randomized pre-test, post-test, control quasi-experimental design. The population of the study was all senior secondary school students in South West Nigeria. The sample comprised 180 Biology students (consisting of 70 males and 110 females) selected from six secondary schools through random and purposive sampling techniques. The instruments used to collect the relevant data for the study was a Biology Concept Test (BCT) which was administered as both pre-test and post-test. The instrument was validated by experts in science education and tests and measurement respectively. Its reliability was ascertained using test-retest method and a reliability coefficient of 0.72 was obtained. The experimental group was treated with a mentoring package involving Classroom Adjunct Instruction Learning Model (CAILM). Data collected were analyzed using Analysis of Covariance (ANCOVA) and Multiple Classification Analysis (MCA). It was discovered from the study that mentoring enhanced the achievement of low-performing students and that female students performed better than their male counterparts in mentoring relationship. Based on the findings of the study, it was recommended (among others) that mentoring should be used by teachers as an adjunct to normal classroom teaching for bringing up slow and poor students to improved level of performance.