Abstract This study aimed to evaluate the efficacy of using ground herb-based phytobiotics and essential oil-based phytobiotics in pig diets on intestinal health and growth performance (GP) of nursery pigs challenged with F18+ Escherichia coli (E. coli). Forty nursery pigs (6.4 ± 0.1 kg) at 21 d of age were individually housed and assigned to 4 dietary treatments in a randomized complete block design, with body weight (BW) and sex as blocking factor. Basal diets were fed to pigs for 28 d in 3 phases. Treatments were NC: basal diet, non-challenged; PC: basal diet, challenged with F18+ E. coli; HP: PC + 1% ground herb-based phytobiotics (Salcochek Pro, Ayurvet Limited, Kaushambi, India); EP: PC + 1% essential oil-based phytobiotics (Liq-biotic, Ayurvet Limited, Kaushambi, India). The GP was recorded for each phase and fecal score (FS) was measured daily. On d 7 post-weaning, the challenged groups were orally inoculated with F18+ E. coli (2.0 × 1010 CFU), the NC treatment received sterile saline solution. On d 28, pigs were euthanized to collect jejunal samples to evaluate intestinal health and relative abundance (RA) of jejunal mucosa-associated microbiota. Data were analyzed using the MIXED procedure on SAS 9.4. The PC increased (P < 0.05) the RA of Prevotellaceae, Lachnospiraceae, and Ruminococcaceae when compared to NC. The HP reduced (P < 0.05) the RA of Veillonellaceae, Prevotellaceae, and Lachnospiraceae when compared to PC. The EP tended to reduce the RA of Streptococcaceae (P = 0.073) and Corynebacteriaceae (P = 0.074) when compared to PC. The PC increased (P < 0.05) occludin and tended to increase (P = 0.096) toll like-receptor-4 (TLR4) when compared to NC. The PC decreased (P < 0.05) average daily gain and average daily feed intake when compared to NC in d 7 to d 28. The PC increased FS (P < 0.05) compared to the HP and EP d 7 to d 11. The HP and EP decreased (P < 0.05) FS when compared to PC during d 7 to d 11 and d 7 to d 18. In conclusion, F18+ E. coli challenge disrupted the jejunal mucosa-associated microbiota, increased TLR4 expression and FS, consequently reduced GP. Both HP and EP phytobiotics supported intestinal morphology during the challenge to F18+ E. coli by supporting enterocyte maturation. The HP and EP treatments exhibited antimicrobial-like effects by altering the jejunal mucosa-associated microbiota and reduced FS during the first two weeks post-challenge. The HP treatment showed potential antioxidant effects.