Chemistry, to a great extent has contributed to the survival of human kind. This is evidenced in such areas as medicine, engineering, agriculture, and transportation. However, the teaching and learning of Chemistry is confronted with myriad of challenges such as under-achievement, low self-efficacy and negative attitude. The Activity, Student-centered, Experiment, Improvisation-Plan, Do, See, Improve (ASEI-PDSI) instructional strategy is a pedagogical model for Strengthening Mathematics and Science Education, and thought to be an intervention measure to these challenges. Hence, this study investigated the effects of ASEI-PDSI instructional strategy on Senior School studentsâ€™ achievement, self-efficacy, and attitude towards Chemistry. The objectives of the study were to examine the: (i) difference in achievement, self-efficacy, and attitude of students exposed to ASEI-PDSI instructional strategy and conventional method; (ii) influence of gender and score levels on studentsâ€™ achievement in Chemistry; and (iii) interaction effects of treatment with gender and score levels on studentsâ€™ achievement in Chemistry.rnThe study adopted a quasi-experimental, non-randomized, pretest, posttest, control group design. The population was all the 40,379 Senior School students offering Chemistry in Ilorin, Nigeria, while the target population was 13,460 Senior School I (SSI) students offering Chemistry. The sample comprised 292 SSI students from four randomly selected co-educational schools in Ilorin, Nigeria. The ASEI-Instructional Package (ASEI-IP) was the stimulus instrument; the Acids, Bases and Salts Achievement Test (ABSAT), Attitude Towards Chemistry Scale (ATCS), and Chemistry Self Efficacy Scale (CSES) were the test instruments. The reliability coefficients of ABSAT, ATCS and CSES were found to be 0.76, 0.68 and 0.73, respectively. The data gathered were analysed using Analysis of Covariance and t-test statistic.rnThe findings of the study were that:rni. a significant difference existed in the achievement of students exposed to ASEI-PDSI instructional strategy (experimental) and those not exposed to ASEI-PDSI instructional strategy (control), (M(experimental) = 25.03 > M(control) = 11.02; F(1, 289) = 238.24, p < .05);rnii. a significant difference existed in the self-efficacy of students exposed to ASEI-PDSI instructional strategy (experimental) and those not exposed to ASEI-PDSI instructional strategy (control), ((M(experimental) = 28.68 > M(control) =25.79; F(1, 289) = 15.32, p < .05);rniii. there was no significant difference in the attitude of students exposed to ASEI-PDSI instructional strategy (experimental) and those not exposed to ASEI-PDSI instructional strategy (control);rniv. there was no significant difference in the achievement of male and female students exposed to ASEI-PDSI instructional strategy;rnv. a significant difference existed in the achievement of low, medium and high scorers exposed to ASEI-PDSI instructional strategy, (M(high) = 27.85 > M(medium) = 24.70 >M(low) = 23.61; F(2, 149) = 5.90, p < .05); andrnvi. there was no significant interaction effects of treatment with gender and score levels on studentsâ€™ achievement in Chemistry.rnThe study concluded that ASEI-PDSI instructional strategy improved studentsâ€™ achievement, self-efficacy and attitude towards Chemistry. This implies that, ASEI-PDSI instructional strategy is very effective for teaching and learning of Chemistry. The study recommended that teachers should adopt ASEI-PDSI instructional strategy to teach Chemistry, especially at the Senior School levels.