The purpose of this study was to evaluate color stability and microhardness of CAD/CAM Cerasmart hybrid ceramic blocks after different immersion times in chlorohexidine and new plant-based mouth wash. Materials and Methods: A total of 120 square discs (10x12x1mm) were cut from 12 hybrid ceramic CAD\CAM blocks (C12, 10x12x15mm, Cerasmart, GC) with a diamond blade (Isomet; Buehler) mounted in a cutting machine. Specimens were divided into three equal groups (n=40) according to immersion media, either, distilled water (DW), chlorohexidine mouthwash (CM) (Orovex, Macro Group pharmaceuticals, Egypt) or Neem (Azadirachata indica) mouthwash (NM) (Neem Mouthwash, Theraneem Naturals, USA). Each group was subdivided into four equal subgroups (n=10) according to immersion time, either one hour and half, three hours, 18 hours or 36 hours. After each time interval, specimens were stored in DW at 37°C till time of evaluation of color change and micro-hardnesss. Results: Two ways ANOVA showed that the immersion media had a statistically significant effect on the VHN and ΔE of Cerasmart , also significance was detected for the effect of immersion time on the VHN and △ E of Cerasmart at a p-value= 0.0001 for both. Conclusion: Long term usage of antimicrobial mouthwashes used in this study (more than one year) should be avoided due to its negative effect on surface microhardness of the used resin based CAD/CAM restorations. Prolonged use of Neem mouthwash had a minimal effect on color change on the used resin based CAD/CAM restorations compared to CHX containing mouth wash (Orovex).