We have studied the interactions of three bile acid-tamoxifen conjugates, lithocholic acid-tamoxifen (LA-Tam(1)-Am), deoxycholic acid-tamwdfen (DCA-Tam(2)-Am), and cholic acid-tamoxifen (CA-Tam(3)-Am), possessing 1-3 tamoxifen molecules having an amine headgroup with model DPPC membranes and compared with N-desmethylated tamoxifen (TamNHMe) using DPH based fluorescence anisotropy, Prodan based hydration, and differential scanning calorimetry studies. DPH based anisotropy studies showed that bile acid-tamoxifen conjugates increase membrane fluidity, which strongly depends on the number of tamoxifen molecules conjugated to bile acid and the percentage of doping of bile acid-tamoxifen conjugates in the DPPC membranes. The order of membrane fluidity of the coliposomes from bile acid-tamoxifen conjugates and DPPC lipids in gel phase was found to be CA-Tam(3)-Am > DCA-Tam(2)-Am > LA-Tam(1)-Am > TamNHMe. Incorporation of bile acid-tamoxifen conjugates showed an unusual complex behavior of membrane hydration, as evident from Prodan based hydration studies. Temperature dependent study showed incorporation of LA-Tam(1)-Am and DCA-Tam(2)-Am conjugates decreases membrane hydration with an increase in temperature up to the phase transition temperature (T-m). Differential scanning calorimetry studies showed a decrease in phase transition temperature (T-m) upon an increase in the percentage of doping of TamNHMe and CA-Tam(3)-Am, whereas LA-Tam(1)-Am and DCA-Tam2-Am do not cause a major change in the phase transition temperature (T-m) of DPPC liposomes. These studies showed the differential behavior of bile acid tamoxifen conjugates regulating the membrane fluidity, hydration, and phase transition of model membranes depending upon the percentage of doping and tamoxifen conjugation to bile acids.