The use of a native directing group to promote C-H activation is highly desirable. Herein, we report a method of native carboxyl-assisted, Pd(II)-catalyzed ortho-C-H acetoxylation of both hydrocinnamic and phenylacetic acids that can be found in many biologically active molecules as the key moieties. Based on the broad scope and the application potential showcased with drug molecules, it is anticipated that this C-H acetoxylation reaction will find attractive applicability in future synthetic endeavors.