Novel multifunctional poly(ε-caprolactone)- gelatin encapsulating upconversion core/shell silica nanoparticles (NPs) composite fibers as dual drugs delivery system (DDDS), with indomethacin (IMC) and doxorubicin (DOX) releasing in individual release properties, have been designed and fabricated via electrospinning process. Uniform and monodisperse upconversion (UC) luminescent NaYF4:Yb3+, Er3+ nanocrystals (UCNCs) were encapsulated with mesoporous silica shells, resulting in the formation of core/shell structured NaYF4:Yb3+, Er3+@mSiO2 (UCNCs@mSiO2) NPs, which can be performed as DOX delivery carriers. These UCNCs@mSiO2 NPs loading DOX then were dispersed into the mixture of poly(ε-caprolactone) (PCL) and gelatin-based electrospinning solution containing IMC, followed by the preparation of dual drug-loaded composite fibers (DDDS) via electrospinning method. The drugs release profiles of the DDDS were measured, and the results indicated that the IMC and DOX released from the electrospun composite fibers showed distinct properties. The IMC in the composite fibers presented a fast release manner, while DOX showed a sustained release behavior. Moreover, the UC luminescent intensity ratios of 2 H11/2/4 S3/2−4 I15/2 to 4 F9/2−4 I15/2 from Er3+ vary with the amounts of DOX in the system, and thus drug release can be tracked and monitored by the luminescence resonance energy transfer (LRET) mechanism.