The investigation examined the consequences of design-based learning integrated with the educational neuroscience instructional model (DEN) and conventional instructional model (CIM) for tenth-grade students’ learning outcomes, executive function, and learning stress. Since the physics curriculum is planned to prepare students for discovering complex scientific concepts through real-life experience, the use of the DEN model is necessary to measure its efficiency. The cluster random sampling method was used to select 63 out of 494 tenth-grade students from Numsomphittayakhon School, Thailand. The researcher administered seven tests and employed the pre-test and post-test control group research design. The experimental and control groups were taught using DEN and CIM, respectively. The data were analyzed by repeated measures of multivariate analysis of variance to study the consequences of both instructional models. The results indicated that students from both groups seemed to demonstrate no significant difference in all the pre-tests on the dependent variables before the treatment with the instructional models. However, MANOVA analysis discovered that the experimental group’s physics learning outcomes and executive functions were better than the control group. Moreover, students from the experimental group seemed to have a lower learning stress level than those from the control group. The results have successfully contributed to contemporary awareness of the efficiency of the DEN model to promote student learning outcomes and executive functions and reduce students’ learning stress. Conventional instructional model, educational neuroscience instructional model, executive functions, learning outcomes, learning stress