The core purpose of integrating inquiry-based learning strategies into STEM activities is to create a challenging learning environment that stimulates students’ active learning, thereby effectively enhancing their interest in learning, thinking skills, and practical application abilities. To achieve these goals, developing more technology-assisted tools and platforms to improve teaching efficiency and enrich the learning experience becomes crucial. Therefore, this research developed InquiryGPT, which guides students through the POEE inquiry process by imposing limitations, facilitating dialogue, and providing feedback, while avoiding over-reliance on ChatGPT. This promotes the cultivation of higher-order thinking skills through interactions with InquiryGPT, thereby enhancing students’ knowledge construction and understanding. This study, based on the Technology Acceptance Model (TAM), examined the effectiveness of InquiryGPT. The results showed no significant difference between InquiryGPT and ChatGPT in terms of perceived usefulness and perceived ease of use. Additionally, through analysis of covariance (ANCOVA), the study further analyzed the impact of InquiryGPT on students’ higher-order thinking skills and learning scores, proving that it significantly enhances students’ creativity, problem-solving abilities, critical thinking, and knowledge construction.