Context: Sesamol, a potential antioxidant with marked anticancer potential suffers from issues of extensive tissue distribution and local gastric irritation on oral administration. Objective: To develop multiunit gastro-retentive floating beads (S-FBs) for localised and prolonged release of sesamol to treat gastric cancers. Materials and methods: S-FBs prepared using calcium carbonate, sodium alginate and hydroxypropylmethyl cellulose (HPMC) in different proportions, were characterised and evaluated in vivo in N-methyl-N-nitro-N-nitroguanidine-induced gastric cancer in rats. Single oral dose plasma pharmacokinetic study was also performed for free sesamol and S-FBs. Results and discussion: Restraining sesamol in floating beads, significantly lowered the release (diffusion controlled) rate, increased t(50%) (31 times) and reduced its in vivo clearance (> 1.5 times). Preclinical evaluation showed S-FBs (10 mg/kg) to be significantly better than free sesamol and better/equivalent to methotrexate (2 mg/kg). Conclusion: Most of the natural phytochemical or antioxidants show pretreatment effectiveness. We, however, developed and established S-FBs for sustained curative effect.