Platelets are primarily responsible for sensing vascular damage and mediating hemostasis and thrombosis. They can also function as immune cells by utilizing their various surface receptors, adhesion molecules, and granule content filled with immunomodulatory effector molecules. By detecting and binding to bacterial pathogens via various receptors—both canonical hemostatic receptors like αIIbβ3, GPIb, GPVI, and P2Ys, as well as immune-related receptors including toll-like receptors (TLRs), FcγRIIa, and the complement receptor gC1q-R—platelets can be activated directly or indirectly by bacteria. Bacterial-activated platelets release immunomodulatory mediators such as defensins, chemokines, and growth factors. These mediators can act as direct microbicides or modulate immune responses by signaling other immune cells, e.g., neutrophils, monocytes, macrophages, and T and B cells, to assist in host defenses or promote inflammation. Despite lacking nuclei, platelets are adept at performing diverse cell biological processes such as endocytosis and exocytosis, autophagy and proteasomal degradation, pyroptosis, and inflammasome activation, antigen presentation, and cross-presentation upon engaging with pathogenic bacteria. During sepsis, when bacterial infections induce systemic host immune responses and organ failure, platelets are critical in regulating immune responses, thrombosis, coagulopathy, and disseminated intravascular coagulation (DIC). Sepsis-induced platelet clearance and decreased production lead to thrombocytopenia, an independent risk factor for poor clinical outcomes and mortality in septic patients. Overall, platelets are first responders to bacterial infections, intimately interact with the immune system, and are critical in coagulopathy and DIC, all of which ultimately influence disease progression and patient outcomes.