This paper presents an approach for designing a novel tooth profile of harmonic drives, which is composed of two pieces of curves, hypocycloid and epicycloid, generated by the rolling circles with appropriate radii. Compared with the conventional double-circular-arc or cycloidal tooth profile of harmonic drives, the tooth profile is characterized by full conjugation, more number of engaged teeth, and can be expressed analytically, etc. Firstly, the generation of the cycloids are briefly described, and then their conjugate criterion is investigated systematically based on Camus’s theorem. Secondly, the tooth profile equations for the circular spline and flexspline are established and the deformed neutral curve equation is derived. Next, the contact properties among the tooth profiles, including the line of action, meshing angle, etc., are studied systematically. Finally, a finite element model and a physical prototype for the harmonic drive with the tooth profile are developed, respectively. The effectiveness of the design method is verified by the contact performances simulation. The research may provide a new thought for the innovative design of harmonic drives with full conjugate tooth profile.