Platelets have many functions in the body but undeniably, their primary role is to stop bleeding (hemostasis). While this component can protect the body from blood loss, it can contribute to the development of other critical conditions, such as atherosclerosis and its complications. This knowledge is essential for the development of new treatments that reduce the risk of blood clots and improve the prognosis of patients with cardiovascular diseases. In particular, a good understanding of these mechanisms pave the way for the invention of drugs that selectively target platelets, thereby controlling their excessive activity without affecting the original protective function. In this study, the antiplatelet activity of newly synthesized fluorinated 3-phenyl-2-isoxazoline-5-carboxamides was investigated. All compounds demonstrated the ability to suppress the aggregation ability of platelets. Increasing the concentration of the active substance from 1 to 25 mmol/L led to an increase in the inhibitory power of the effectors. Thus, this study has, for the first time, revealed pronounced selectivity of certain 2-isoxazoline amide derivatives toward either adenosine diphosphate (ADP)- or collagen-induced aggregation, with the direction of selectivity determined by the position of fluorine atoms on the phenyl ring. It was also established that the functional group at the 5-position of the heterocycle influences activity, and the advantage of amides and esters over free acids was demonstrated. Among the studied compounds, the most active were 3-(3-fluorophenyl)-2-isoxazoline-5-carboxamide (in the ADP test) and 3-(3,5-difluorophenyl)-2-isoxazoline-5-carboxamide (in the collagen test).