Probiotics are often advised to be taken separately from antibiotics due to their sensitivity to antibiotic activity and gastrointestinal (GI) stress. However, spores, as next-generation probiotics, may withstand concurrent use with antibiotics due to their unique structural adaptations. This study systematically evaluated the survival rates and morphological changes of spores exposed to 10 clinically relevant antibiotics in simulated gastric/intestinal fluids, exploring their feasibility for co-administration with antibiotics. Survival rates of spores were tested against 10 antibiotics across four classes (β-lactams, macrolides, aminoglycosides, and tetracyclines) in simulated GI fluids. Time-kill curves analyzed spore survival over 0-4 h, while scanning electron microscopy (SEM) observed spore wall integrity and morphological changes under different conditions. The spore survival rates remained >89% in intestinal fluid and >60% in gastric fluid across all antibiotics. SEM revealed gastric acid and proteolysis increased spore wall fragmentation, reducing resistance, whereas the intestinal environment preserved spore integrity. This study was the first to demonstrate that spores can survive simultaneous exposure to antibiotics in the gastrointestinal tract, challenging traditional probiotic usage guidelines. The findings support their co-administration with antibiotics to simplify dosing regimens and improve medication adherence. Such an approach advances antimicrobial stewardship by optimizing therapeutic strategies for antibiotic-probiotic combinations.