Curcumin, the yellow pigment from the rhizoma of Curcuma longa, is a widely studied polyphenolic compound which has a variety of biological activity as anti-inflammatory and antioxidative agent. Genistein one of the flavonoids found in soybean and chickpeas inhibits DNA strand breaks acting as a direct scavenger of reactive oxygen species. Human serum albumin (HSA) with high affinity binding sites is a major transporter for delivering several endogenous compounds and drugs in vivo. The aim of this study was to examine the interactions of curcumin and genistein with human serum albumin at physiological conditions, using constant protein concentration and various pigment contents. FTIR, UV-Visible, CD and fluorescence spectroscopic methods were used to analyse drug binding mode, the binding constant and the effects of pigment complexation on HSA stability and conformation. Structural analysis showed that curcumin and genistein bind HSA via polypeptide polar groups with overall binding constants of K(curcumin)=5.5 (+/-0.8)x10(4)M(-1) and K(genistein)=2.4 (+/-0.40)x10(4)M(-1). The number of bound pigment (n) is 1.33 for curcumin and 1.49 for genistein. The HSA conformation was altered by pigment complexation with reduction of alpha-helix and increase of random coil and turn structures suggesting a partial protein unfolding.