Avian colibacillosis, caused by avian pathogenic Escherichia coli (APEC) serotype O78, poses a major threat to poultry production through high morbidity, mortality, and economic losses. While antibiotics such as ciprofloxacin remain the mainstay of treatment, increasing antimicrobial resistance necessitates evaluation of alternative therapies. This study aimed to compare the antibacterial, antioxidant, and histopathological effects of curcumin, garlic, green tea and some combinations against experimental E. coli O78 infection in broiler chickens, with ciprofloxacin used as a reference standard. A total of 240 chicks were randomly allocated into eight groups, including negative, positive controls, curcumin, green tea, garlic, ciprofloxacin, and combination regimens. Birds (except negative control) were orally challenged with E. coli O78 at day 14. Clinical signs, mortality, growth performance, lesion scores, histopathological changes, and antioxidant markers (CAT, SOD) were assessed. The positive control group showed severe colibacillosis with marked hepatic damage, while all phytogenic treatments produced clear clinical and histopathological improvement. Curcumin, green tea, and garlic reduced lesion severity by Day 19 and showed further healing by Day 25, with curcumin + green tea offering notable early protection. Ciprofloxacin combination with phytogenics at half dose achieved the greatest lesion resolution. Antioxidant results showed higher CAT and SOD activities in curcumin-based treatments, while ciprofloxacin and infected controls had the lowest values. Histopathological examination revealed that birds treated with the triple combination (G8) and dual-phytogenics (G5) exhibited significantly improved liver architecture with minimal inflammatory infiltration compared to the severe hepatic damage observed in the positive control (G2) and enhanced antioxidant status in E. coli–infected birds so it can enhance or complement conventional antibiotic therapy.