This chapter describes the use of fuzzy set theory and intuitionistic fuzzy set theory in DNA sequence comparison. It also shows an indirect application of fuzzy set theory in comparing protein sequences. In fact, protein sequences consist of 20 amino acids. The chapter shows how such amino acids can be classified in six different groups. These groups are obtained purely from theoretical considerations. These are entirely different from the known groups of amino acids based on biological considerations. Also it is known how these classified groups of amino acids help in protein sequence comparison. The results of comparison differ as the groups differ in number and their compositions. Naturally it is expected that newer results of comparison will come out from such newer classified groups of amino acids obtained theoretically. Thus fuzzy set theory is also useful in protein sequence comparison. © 2017, IGI Global.