The effect of substituting K2O for Na2O on the physical and chemical properties of 15 glasses in the system Na2O–K2O–CaO–P2O5–SiO2 was studied for three series: low (52 mol% SiO2), medium (60 mol% SiO2) and high (66 mol% SiO2) silica. The SiO2 content expressed as weight-% varied from 46 to 64 wt%, thus suggesting that the compositions were either bioactive or biocompatible. The crystallization tendency and sintering behavior were studied using differential thermal analysis and hot stage microscopy. Formation of silica- and hydroxy-apatite-rich layers were studied for glass plates immersed in static simulated body fluid. The release of inorganic ions into Tris buffer solution was analyzed using inductively coupled plasma optical emission spectrometer in dynamic and static conditions. Substitution of K2O for Na2O suggested mixed alkali effect (MAE) for the thermal properties with a minimum value around 25% substitution. With increased share of K2O in total alkali oxides, the hot working window markedly expanded in each series. Silica and hydroxyapatite layers were seen only on the low silica glasses, while a thin silica-rich layer formed on the other glasses. In each series, greater dissolution of alkali and alkali earth ions was seen from K-rich glasses. Clear MAE and preferential ion dissolution were recorded for medium and high silica series, while for low silica glasses, the initial MAE dissolution trends become rapidly covered by other simultaneous surface reactions. MAE enables designing especially low silica bioactive glasses for improved hot working properties and medium and high silica glasses for controlled dissolution.