Antimicrobial packaging films have been widely used in various applications. However, because of concerns regarding safe food and consumer demands for preservative-free products, the antimicrobial agents applied to packaging have to be highly effective and the leaching effect is not allowed. In the present work, the antimicrobial agent polyhexamethylene guanidine hydrochloride was compounded with starch to prepare antimicrobial thermoplastic starch (ATPS). ATPS was then melt-blended with linear low-density polyethylene (LLDPE) to prepare the novel antimicrobial packaging film. The resultant LLDPE/ATPS films exhibited excellent antimicrobial properties against Escherichia coli in the shaking-flask test. The ring-diffusion test further confirmed the nonleaching effect of the films. However, the addition of ATPS decreased the crystallinity of LLDPE. Both rheological analysis and scanning electron microscopy images indicated that a high ATPS content might result in poor compatibility even in the presence of a compatibilizer.