This book constitutes the proceedings of the 21st International Conference on Smart Card Research and Advanced Applications, CARDIS 2022, which took place in November 2022. The conference took place in Birmingham, United Kingdom.The 15 full papers presented in this volume were carefully reviewed and selected from 29 submissions. They were organized in topical sections named: physical attacks; physical countermeasures; protecting AES; evaluation methodologies; attacking NTRU; next-generation cryptography.