This paper attempted to evaluate the impact of educational multimedia based on Gagné’s Instructional Systems Design (ISD) on learning and retention of Natural Sciences among sixth grade students with intellectual disability. The methodology involved a quasi-experimental procedure, pretest-posttest and a control group. The population included all sixth grade female students with intellectual disability studying at special education centers of Khorramabad, Iran, during the academic year 2014-2015. Using convenient sampling, 30 students were selected and then randomly divided into two groups. The instrument used in this study was a researcher-made learning and retention quiz. The learning pre-test was administered by the researcher for both experimental and control groups. Then, the experimental group was trained through eight sessions using multimedia devices based on Gagné’s model, while the control group received the conventional treatment. Post-test was administered on both groups. The researcher administered the retention quiz on students two weeks after the completion of course. Statistical methods were employed at descriptive and inferential levels to analyze the statistical data. The findings suggested a significant difference between the experimental and control groups in terms of learning and retention rate. In fact, the experimental group achieved better learning and retention.