Glycerol monooleate (GMO) matrix was found to be a gastro-retentive carrier system suitable for both polar and as well as non-polar drugs. Chlorpheniramine maleate (CPM) and diazepam (DZP) were used as model drugs. Effect of PEG 4000, PEG 10000, and stearic acid on floatability and release profile was studied. Water uptake increased with increase in the loading of polar drug (CPM) and decreased with non-polar drug (DZP). Similar effect was found to occur in case of drug release. PEGs increased the release up to certain concentration and decreased thereafter. Drug release decreased linearly with concentration of stearic acid. The type and extent of mesophases formed were significantly affected by the nature of drug, excipients and their concentration. Thus the selection of suitable excipients depending on polarity of drug, could help to modulate the floatability and release profile from GMO matrices.