Bioinformatics and computational biology have become indispensable in modern biological research, yet introductory resources remain scarce. FILTERED, an innovative online educational tool that introduces high school students to fundamental bioinformatics concepts through engaging puzzle-based gameplay, was developed to address this gap. Set against the backdrop of a fictitious global pandemic, FILTERED employs comic-book-style graphics and multi-level puzzles to simulate the application of computational tools in analyzing DNA sequences and solving biological problems. Unlike traditional bioinformatics modules focusing on programming skills, FILTERED aims to develop a conceptual understanding of bioinformatics processes. The game covers key concepts such as quality scoring, sequence alignment, conservation analysis, comparative genomics, and variant identification. A comprehensive evaluation of FILTERED revealed statistically significant improvements in students’ bioinformatics knowledge across various educational settings. While the study observed an unexpected decrease in self-reported interest in bioinformatics careers post-gameplay, positive feedback from students and teachers regarding engagement and enjoyment suggests FILTERED’s potential as a valuable resource in science education. This paper discusses the game’s design, implementation, and evaluation results, highlighting its effectiveness in enhancing bioinformatics education and addressing the growing demand for computational biology skills in an accessible manner.