Purpose <p>The efficient clinical utilization of Berberine (BRB), a natural alkaloid, could be hampered by its poor dissolution performance in the gastric fluid and by the intestinal glycoprotein mediated efflux. Therefore, formulations that enhance BRB dissolution with prolonged gastric retention may be beneficial. In this work, we sought to improve the dissolution performance of BRB by its complexation with carrageenan (CRG), a hydrophilic polyelectrolyte.</p> Methods <p>The optimum ratios of the complexation using λ and κ-CRG were studied by viscosity measurements. The release of BRB from the complexes was assessed in simulated gastric fluid (SGF). The complex with enhanced BRB release, namely BRB-κ-CRG complex, was formulated as hydroxypropyl-methylcellulose floating matrix.</p> Results <p>Compared to BRB-λ-CRG complex and neat BRB, BRB-κ-CRG complex showed a higher and faster rate of BRB release in SGF. Relative to that of BRB, the floating matrix of BRB-κ-CRG complex was shown to release twice as much BRB in a sustained-release zero-order pattern throughout the course of 8&#xa0;h of dissolution in SGF.</p> Conclusion <p>The outcomes of the work are highly beneficial for further investigation of natural alternatives that target gastric related conditions.</p>