Foxtail millet (Setaria italica L.) is an important commercial crop in north China, especially northwest China. However, the uneven distribution of precipitation induce severe seasonal drought and drought seriously limits the yield production of foxtail millet. To clarify physiological characteristics of different genotypes of foxtail millet cultivars in response to drought stress, drought resistance cultivar (Yugu 1) and drought sensitive cultivar (An 04) and xiaomi were selected as materials to detect and compare the photosynthetic parameters, chlorophyll content, non-structure carbohydrate, gene expression of beta-amylase (SiBAM1) at one or three growth periods (jointing, anthesis and ten days after anthesis stage) through a pot experiment carried out in the rainproof shed. Results showed that under normal soil water condition, the An 04 held higher grain yield than Yugu1 cultivar. Drought stress severely restricted the yield formation of two cultivars. while the yield of An 04 was reduced by 71.2%, and that of Yugu 1 was reduced by 56.0%. And Yugu1 cultivar had higher grain yield that An 04 under drought condition. Under normal soil water conditions, An 04 had a higher net photosynthetic rate than Yugu 1 (P<0.05). while under drought stress, the leaf net photosynthetic rate of Yugu 1 was significantly higher than that of An 04 at these three detected growth stages. Leaf transpiration rate was consistent with that of leaf photosynthetic rate. However, the Yugu1 held higher leaf relative water content than An 04 under drought condition. Drought stress significantly reduced the chlorophyll a, chlorophyll b and total chlorophyll contents of the two cultivars, while the decrease range of An 04 was greater than that of Yugu 1 especially at anthesis stage. Drought stress significantly increased the soluble sugar content in Yugu 1 leaves at the stage of jointing and anthesis stage, while there was no significant change in the soluble sugar content in the leaves of An 04. Drought stress significantly increased the expression level of SiBAM1 in Yugu 1 gene. Application of α-cyclodextrin, an inhibitor of β-amylase activity, further increased the inhibition of drought on the growth of millet xiaomi, and the contents of leaf soluble sugar and proline decreased significantly compared with none α-cyclodextrin application. In summary, drought stress induced the increase of β-amylase gene expression and β-amylase activity in foxtail millet, which could take part in hydrolyzing starch into soluble sugar, and the increased soluble sugar played an important role in improving drought resistance of foxtail millet.