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In this study, we characterize the biodistribution in mice of<jats:italic>Momordica cochinchinensis<\/jats:italic>trypsin inhibitor\u2010II (MCoTI\u2010II), a cyclic three\u2010disulfide\u2010containing peptide that has been used in a number of studies as a drug scaffold. The distribution of MCoTI\u2010II was compared with that of chlorotoxin, which is a four\u2010disulfide\u2010containing peptide that has been used to develop brain tumor imaging agents; dermorphin, which is a disulfide\u2010less peptide; and bovine serum albumin, a large protein. Both MCoTI\u2010II and chlorotoxin distributed predominantly to the serum and kidneys, confirming that they are stable in serum and suggesting that they are eliminated from the blood through renal clearance. Although cell\u2010penetrating peptides have been reported to be able to transport across the blood\u2013brain barrier, MCoTI\u2010II, which is a cell\u2010penetrating peptide, showed no uptake into the brain. The uptake of chlorotoxin was higher than that of MCoTI\u2010II but lower than that of dermorphin, which is considered to have low uptake into the brain. This study provides insight into the behavior of disulfide\u2010rich peptides<jats:italic>in vivo<\/jats:italic>. 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