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This study determined the effect of Desmos Instructional Software on interest in quadratic graphs among secondary school students in Karu, Nasarawa State, Nigeria. A quasi-experimental research design of pre-test, post-test, control group was used in this study. The population of the study comprised 10,543 senior secondary school two (SS2) students in Karu, Nasarawa State. Ninety-two (92) students from two intact classes, of which 44 were male and 48 were female, were made up of 44 students in the experimental group purposively selected and 48 students in the control group randomly picked for this study. Two research questions and two null hypotheses guided the study. The instrument for data collection was the Quadratic Graph Interest Scale (QGIS). The instrument was validated by three experts with an average validity index of 0.84. The reliability of the QGIS was determined using Cronbach Alpha and was found to be 0.89. Descriptive statistics of mean and standard deviation were used to answer the research questions, while inferential statistics of Analysis of Covariance (ANCOVA) was used to test the null hypotheses at a 0.05 level of significance. The findings revealed that Desmos Instructional Software significantly enhanced students’ interest in quadratic graphs, and had no significant difference between male and female students. It was recommended that mathematics teachers integrate Desmos Instructional Software into classroom instruction to improve students’ interest in mathematics.