Natural bioactive compounds have become increasingly important antitumor and antimicrobial agents due to their high therapeutic potential and low systemic toxicity. However, they also have significant drawbacks like nontumor targeting and low bioavailability, which limit their wide therapeutic applications. There is an urgent need for a safe and compatible nanoparticle-mediated drug delivery system for the efficient transport of drug candidates into tumor tissues. In this paper, amine-modified zinc oxide nanoparticles are synthesized to load luteolin. The functionalized nanoparticles exhibit good synergistic effects in terms of antitumor and antibacterial activities. They show significant induction of oxidative stress and antitumor effects, while no significant inhibitory effect on normal cells is observed, suggesting that the nanocomposites have good targeting of cancer cells. Autophagy activation and EMT inhibition effects are studied to explain the good antitumor performances. The prepared nanocomposites are demonstrated to be attractive candidates for cancer therapy.