The use of small peptides for medical purposes has gained great importance in the last decade. Among these molecules are the growth hormone releasing peptides (GHRPs). These substances are highly sought by cheating athletes because of their ergogenic effects. Thus, GHRPs are listed in the World Antidoping Agency Prohibited List and several methods have been developed for their detection in urine samples. Serum is another useful matrix frequently used for anti-doping control. An experimental adaptation of a competitive methodology for GHRPs wide-group detection, previously developed for urine, is reported here using a serum matrix instead. The modifications have been mainly addressed the need to remove endogenous ghrelin (always present in serum) to avoid interference in the competitive binding assay. The modified test was first evaluated using serum spiked with different pure GHRPs (i.e., GHRP-2, GHRP-6 and Hexarelin), then using serum samples from pilot studies in which healthy subjects were treated intravenously with GHRP-2 and intranasally with GHRP-2 and GHRP-6. The results showed the reliability of the modified methodology for the detection of GHRPs in a serum matrix.