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Periodic mesoporous organosilicas (PMOs), reported for the first time in 1999, constitute a new branch of organic-inorganic hybrid materials with high-ordered structures, uniform pore size and homogenous distribution of organic bridges into a silica framework. Unlike conventional mesoporous silicas, these materials offer the possibility to adjust the surface (hydrophilicity/hydrophobicity) and physical properties (morphology, porosity) as well as their mechanical stability through the incorporation of different functional organic moieties in their pore walls. A broad variety of PMOs has been designed for their subsequent application in many fields. More recently, PMOs have attracted growing interest in emerging areas as biology and biomedicine. This review provides a comprehensive overview of the most recent breakthroughs achieved for PMOs in biological and biomedical applications.