The current study investigated the effectiveness of self-regulatory instruction developed based on guided inquiry on 11th grade students' use of learning strategies and achievement in chemistry, compared to traditionally designed chemistry instruction. Additionally, the self-regulatory processes in which students engaged and the development of these processes over the course of the study were examined. For this purpose, mixed-method design was employed. In total, 78 students participated in the study: 38 students in the experimental group and 40 students in the control group. Additionally, four students from each classroom were selected as focal students, using the maximum variation sampling method. Quantitative data were collected using Chemistry Achievement Test and Cognitive and Metacognitive Strategies Scale; qualitative data were obtained through journals and think-aloud protocols. Five dependent variables were studied: achievement in chemistry, and the four learning strategies of rehearsal, elaboration, organization, and metacognitive self-regulation. A mixed multivariate analyses of variance was run to analyze the quantitative data and the deductive method was used to analyze the qualitative data. Quantitative results indicated a slight improvement in student achievement in the experimental group and no significant difference regarding learning strategies. However, analyses of think-aloud protocols revealed that students in the experimental group used metacognitive strategies more often, which were associated with self-regulated learning, and in turn achieved more-gave more correct responses and/or provided more complete scientific explanations-compared to the students in the control group.