INTRODUCTION: Many human tumours have hyperactive signal transducer and activator of transcription 3 (STAT3, positioning it as a prime target for natural compounds with anticancer properties. This study investigated three small-molecule STAT3 inhibitors derived from MATERIAL AND METHODS: The compounds were explored through virtual screening and molecular dynamics (MD) simulations to understand the intracellular processing of activated STAT3. The biological effects of these STAT3 inhibitors on human cancer cells were assessed via simulation. Further, RESULTS AND DISCUSSION: It is revealed through results that active components in these compounds inhibited cancer cell migration and invasion and suppressed the proliferation of noncancer cells. Moreover, these natural compounds from