In this work, a novel anti-smudge coating system was developed by using hydroxyl-terminated hyperbranched polyester as a coating precursor, mono-hydroxyl-terminated poly(dimethylsiloxane) (PDMS) as an anti-smudge agent, and hexamethylene diisocyanate trimer as a curing agent. The resultant coatings with 0.5 wt % PDMS content incorporated are highly transparent and liquid repellent. They exhibit striking repellency against various liquids and display remarkable self-cleaning performance. Water, hexadecane, salt solution, strong alkali solution, strong acid solution, pump oil, and crude oil could slide off the coated surface without leaving any traces, and the dirt on the coated surface could be readily removed by water or oil. Besides, these coatings show potential application for anti-fingerprint and anti-graffiti due to the exceptional repellency of coated surface against artificial fingerprint liquid, oil-based ink, paint, and water-based smudge. Furthermore, they also possess superb chemical shielding ability and thus endow substrates with remarkable protection against exposure to harsh chemical conditions. Moreover, these coatings are mechanically robust against extensive abrasion, impact, and bending without compromising anti-smudge properties, and they also exhibit excellent adhesion to various substrates. Therefore, these newly developed coatings have tremendous potential for widespread applications.