Aim The aim of this study was to explore the caries features in hypoplastic Amelogenesis Imperfecta (AI) patients. Materials and methods A cross-sectional study was performed including 28 patients, 14 with hypoplastic AI and 14 controls for whom Decayed (D), Missed (M) and Filled (F) Teeth (T) were checked for a DMFT index evaluation. Twenty-eight saliva samples, 4 bacterial plaques and 19 teeth were used. Decayed teeth were observed under polarized light and scanning electron microscopy. Salivary pH was measured and saliva bacterial strains were biochemically identified and confirmed by PCR. Bacterial adhesions to tooth surfaces were observed by Scanning Electron Microscopy (SEM) and evaluated by colony enumeration after in vitro culture of Streptococcus mutans and Lactobacillus casei with dental fragments. Results DMFT indexes were significantly lower in AI patients (mean DMFT = 0.8) compared to controls (mean DMFT = 2.9). Decayed teeth revealed sclerotic, demineralized, invaded and disintegrated zones in dentine. Dental plaques were rich with filamentous bacteria in AI patients. Oral microbiotome of the saliva showed a low rate of Streptococci and a significant high level of Bacillus spp, Enterococcus faecalis and Enterococcus faecium in AI patients. In vitro study showed a significant high adhesion of Lactobacillus casei and a weak adhesion of Streptococcus mutans on AI dental hard tissues. Conclusion Our study showed that hypoplastic AI patients have (i) a low DMFT index, (ii) an alkaline pH of saliva enriched with Bacillus spp, Enterococcus faecalis and Enterococcus faecium and (iii) dental tissues more easily invaded by Lactobacilli than Streptococci. The combination of these bacteria seems to give AI patients protection against dental caries.