This study investigated the effect of Ethnoscience instruction and moderating effects of school location and parental educational status on students' attitude to science. It employed pretest-posttest, non-equivalent control group quasiexperimental design. Participants were 352 Junior Secondary School 1 (aged 9-12 years) students from two schools, each in urban and rural areas of Ìbàdàn, southwestern Nigeria. Instruments used are: Teachers Instructional Guide on Ethnoscience instruction, Teachers Instructional Guide on Modified Lecture Method and Attitude Toward Science Scale (r = 0.86). Three null hypotheses were tested at 0.05 level of significance. Data were analyzed using Analysis of Covariance. Significant main effect of treatment on attitude to science (F(1, 347) = 296, p < 0.05) was recorded, with Ethnoscience instruction group performing better than the Modified Lecture Method group. Effect size of treatment was strong (?[superscript 2] [subscript p] = 0.46). Also recorded were significant main effects of school location (F(1, 347) = 10.2, p < 0.05) and parental educational status (F(1, 347 = 3.37), p < 0.05) on students' attitude to science with weak effect sizes (?[superscript 2] [subscript p] = 0.029 and ?[superscript 2] [subscript p] = 0.019 respectively). Learners in rural schools performed better than those in urban schools and those from lowly educated parents had better performance than highly educated parents. Ethnoscience instruction promoted learners' attitude to science. Therefore, its use in educational instruction, especially among traditional science learners, should be explored.