Optical biosensors based on plasmonic sensing schemes combine high sensitivity and selectivity with label‐free detection. However, the use of bulky optical components is still hampering the possibility of obtaining miniaturized systems required for analysis in real settings. Here, a fully miniaturized optical biosensor prototype based on plasmonic detection is demonstrated, which enables fast and multiplex sensing of analytes with high‐ and low molecular weight (80 000 and 582 Da) as quality and safety parameters for milk: a protein (lactoferrin) and an antibiotic (streptomycin). The optical sensor is based on the smart integration of: i) miniaturized organic optoelectronic devices used as light‐emitting and light‐sensing elements and ii) a functionalized nanostructured plasmonic grating for highly sensitive and specific localized surface plasmon resonance (SPR) detection. The sensor provides quantitative and linear response reaching a limit of detection of 10⁻⁴ refractive index units once it is calibrated by standard solutions. Analyte‐specific and rapid (15 min long) immunoassay‐based detection is demonstrated for both targets. By using a custom algorithm based on principal‐component analysis, a linear dose–response curve is constructed which correlates with a limit of detection (LOD) as low as 3.7 µg mL⁻¹ for lactoferrin, thus assessing that the miniaturized optical biosensor is well‐aligned with the chosen reference benchtop SPR method.