Biodegradable silica microparticles (SiMPs) are a promising carrier matrix for controlled ocular drug delivery. In tissues, SiMPs degrade into silicic acid (SiA), a soluble inorganic weak acid. This study evaluated the in vitro toxicity and tolerability of SiA and SiMPs’ precursor, tetraethyl orthosilicate (TEOS), in human corneal epithelial cells (HCE-2) and retinal pigment epithelial cells (ARPE-19). Cells were exposed to serial dilutions of SiA and TEOS. Cell viability was assessed after 24, 48, and 72 h using the alamarBlue assay, while membrane integrity was analyzed through LDH release. To evaluate cellular stress from SiA and TEOS, levels of pro-inflammatory, apoptosis, and heat shock stress response markers were measured. Neither viability assay revealed significant differences in survival rates between the control group and 30 µg/mL SiA in ARPE-19 and HCE-2 cells at all time points. ARPE-19 viability decreased with low SiA concentrations, but this was not supported by LDH release or caspase-3 activation. Inflammatory markers IL-6, IL-8, and MCP-1 secretion or heat shock protein 70 expression levels were not changed in either cell line in response to SiA. Conversely, TEOS reduced cell viability at high concentrations (0.6–2.4 mg/mL) and affected the cytokine response in both cell lines. Our results indicate that both cell lines can tolerate SiA concentrations up to 30 µg/mL. In contrast, TEOS showed toxicity at concentrations above 0.6 mg/mL, which greatly exceeds expected levels in the SiMP formulation. These findings support the use of SiMPs as drug delivery vehicles in ophthalmic formulations.