In this study the influence of an enantiomeric co-former and the preparation method on the solid-state properties and physical stability of co-amorphous systems were investigated. Co-amorphous systems consisting of indomethacin (IND) and chiral tryptophan (TRP) as co-former in its two enantiomeric forms, as racemate, and as conglomerate (equimolar mixture of D- and L-TRP) were prepared. Co-amorphization was achieved by ball milling (BM) and spray drying (SD). The effects of chirality and preparation method on the solid-state properties and physical stabilities of the systems were investigated by XRPD, FTIR and mDSC. Differences in the BM process were caused by the enantiomeric properties of the co-former: The IND/TRP conglomerate (IND/TRPc) turned co-amorphous after 60 min. In contrast, co-amorphization of IND/L-TRP and IND/D-TRP required 80 min of ball milling, respectively, and the co-amorphous IND/TRP racemate (IND/TRPr) was obtained only after 90 min of ball milling. Although the intermolecular interactions of the co-amorphous systems prepared by BM and SD were similar (determined by FTIR), the T_g values differed (∼87 °C for the ball milled and ∼62 °C for the spray dried systems). The physical stabilities of the ball milled co-amorphous systems varied between 3 and 11 months if stored at elevated temperature and dry conditions, with the highest stability for the IND/TRPc system and the lowest stability for the IND/TRPr system, and these differences correlated with the calculated relaxation times. In contrast, all spray dried systems were stable only for 1 month and their relaxation times were similar. It could be shown that the chirality of a co-former and the preparation method influence the solid-state properties, thermal properties and physical stability of IND/TRP systems.