Cathepsins, also known as lysosomal cysteine peptidases, are members of the papain-like peptidase family, involved in different physiological processes. In addition, cathepsins are implicated in many pathological conditions. This report describes the synthesis and evaluation of a series of N-arylanthranilic acids, acridones, and 4-quinolinones as inhibitors of cathepsins V and L. The kinetics revealed that compounds of the classes of acridones are reversible competitive inhibitors of the target enzyme with affinities in the low micromolar range. They represent promising lead candidates for the discovery of novel competitive cathepsin inhibitors with enhanced selectivity and potency. On the other hand, 4-quinolinones were noncompetitive inhibitors and N-arylanthranilic acids were uncompetitive inhibitors.