This study aims to describe the implementation of learning, students' science process skills, and students' responses after participating in learning with an ethnoscience-based guided inquiry learning model on the material of the human excretory system. This research method uses a Quasi Experimental Design with the design "The Only Pretest-Posttest Control Group Design" whose research targets are students in class VIII-D SMPN 16 Surabaya as the experimental class, class VIII-A as the control class, each of which consists of 30 participants. Data obtained by observation, test, and questionnaire methods were then analyzed descriptively quantitatively. The results showed that the proportion of learning implementation was 87.94 in the experimental class for 3 meetings, said to be in the practical and effective category. In the experimental class, science process skills increased significantly with the aspect of predicting and concluding the N-Gain value, namely 0.8, which increased with the high criteria, drawing conclusions, namely 0,7, which experienced an increase in the degree of high criteria, and the observing aspect, which was 0,4 with the criteria moderate rise. Students responding to the implementation of the ethnoscience-based guided inquiry learning model to improve science process skills by 86.84% were categorized as very good. Based on the description above, it can be interpreted that the application of the ethnoscience-based guided inquiry learning model can improve students' processing skills in the material of the human excretory system.