The guanidine group defines chemical and physicochemical properties of many compounds of medical interest and guanidine-containing derivatives constitute a very important class of therapeutic agents suitable for the treatment of a wide diseases spectrum [1]. The coupled thermogravimetry - differential scanning calorimetric (TGDSC) technique has been employed in order to investigate the thermal behavior of four guanidine derivatives compounds, namely: arginine, creatine anhydrous, creatine monohydrated and creatinine e-beam irradiated. Arginine is involved in the division of cells, in the removal of ammonia from the body, in immunity mechanism and in hormone secretion. Creatine is an amino acid produced in small amounts by some organs and stored in supplement used to enhance an individual’s ability muscles. The results were compared with similar ones for the same non-irradiated compounds. The samples were irradiated with e-beams at dose range of (25–100) kGy at room temperature. The phase transition points (melting) and decomposition processes occurring by heating were put in evidence from DSC thermograms in the temperature range between ambient to 450°C. The effects of e-beam irradiation on thermal parameters and their variation as a function of irradiation dose were analyzed. The Fourier transformed infrared (FTIR) was used to highlight the functional groups and hydrogen bonds and their modification related to irradiation. The determined parameters are very useful in characterisation of pharmaceutical compounds and characterisation of intermediates and products. Taking in account that all compounds presented in our contribution are used as drugs or nutritional supplements, the processes occurring during heating studied by DSC have also importance to assessment the stability regions of drugs as a function of temperature and irradiation dose.