This study aims to compare the effectiveness of a Peer-Led Team Learning (PLTL) model with that of traditional college instruction (TCI) in enhancing the conceptual understanding and reducing both the state anxiety and social anxiety of undergraduate engineering students in a general chemistry course in a quasi-experimental design. 128 engineering students taking the course participated in the study. One of the course sections was randomly assigned to the experimental group and the other section was assigned to the control group. Both sections were taught by the same instructor. The control group was instructed using traditional college instruction, while the experimental group was instructed using the PLTL model. Throughout this study, six peer-led chemistry workshops and leader training sessions were performed simultaneously. The General Chemistry Concept Test, the State–Trait Anxiety Inventory, and the Social Anxiety Questionnaire for Adults were administered before and after the treatment to both groups. One-way Multivariate Analysis of Covariance (MANCOVA) indicated that after controlling students’ university entrance scores, trait anxiety scores and pre-test scores of both the General Chemistry Concept Test and state anxiety, the PLTL model was more effective in improving the conceptual understanding and reducing the situational anxiety of engineering students in undergraduate general chemistry. However, it was not so effective in lessening their social anxiety when compared to traditional college instruction.