This study evaluated in vitro the biologic profile of manually polished surfaces of pressed lithium disilicate (LD) ceramic compared to zirconia (Zir) in human gingival fibroblasts. Samples with a 10-mm diameter and 3-mm thickness were used. After manual polishing, the average roughness (Ra) of the samples was measured. The cell proliferation and viability of gingival fibroblasts on the surfaces were assessed at 24, 48, and 96 hours. Additionally, the morphology, cell adhesion, and type III collagen (COLIII) and vimentin (VIM) expression by fibroblasts plated onto these surfaces was analyzed. Polystyrene (Pol) was used as control for all assays. The mean Ra was 0.261 ± 0.053 μm for Zir and 0.345 ± 0.130 μm for LD. Both surfaces presented similar cell proliferation and viability (P > .05). The cell morphology demonstrated that, for both surfaces, the cells were occasionally spindle-shaped, parallel to the direction of the grooves. Compared to Pol, an upregulation of COLIII and VIM gene expression was observed by fibroblasts cultured on Zir and LD at all time points (P < .05). The characteristics presented by LD and Zir surfaces after manual polishing protocol were similar and had biologically favorable performances, thus suggesting LD as a suitable alternative to Zir in the peri-implant region for esthetic purposes.