The interactions of baicalin and wogonoside with human serum albumin (HSA) were studied by fluorescence quenching and ultraviolet-visible absorption spectrometry. The binding constants were obtained by fluorescence quenching of drug with serum albumin. The main acting binding forces of baicalin and wogonoside to serum albumins were hydrophobic force according to the thermodynamic parameters. The effects of metal ions, such as Zn2+, Mg2+, Al3+ and Cu2+ on binding constants were also evaluated. It is not only valuable to reveal the pharmacokinetics, clinical therapy, but also guiding significance for drug design and development of new drugs.