Bioinformatics has significantly advanced RNA-based therapeutics, particularly circular RNAs (circRNAs), which outperform mRNA vaccines, by offering superior stability, sustained expression, and enhanced immunogenicity due to their covalently closed structure. This review highlights how bioinformatics and computational biology optimise circRNA vaccine design, elucidates internal ribosome entry sites (IRES) selection, open reading frame (ORF) optimisation, codon usage, RNA secondary structure prediction, and delivery system development. While circRNA vaccines may not always surpass traditional vaccines in stability, their production efficiency and therapeutic efficacy can be enhanced through computational strategies. The discussion also addresses challenges and future prospects, emphasizing the need for innovative solutions to overcome current limitations and advance circRNA vaccine applications.